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Background: Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease that leads to multiple organ dysfunction. The advent of disease-modifying treatments makes the early diagnosis of SMA critical. Health information literacy is vital for obtaining, understanding, screening, and using health information. Considering the importance of early diagnosis and the challenges in obtaining accurate information on patients with SMA, this cross-sectional study assessed health information literacy among children with SMA and their caregivers in China. Methods: Interviews with the caregivers of 10 patients with SMA were conducted by neurologists specializing in SMA. A questionnaire for evaluating the level of health information literacy was further developed among 145 children with SMA aged 10.0–120.0 months, with the average age of 81.9 months, and their caregivers. Parameters, such as the age at the onset of the first symptom and time from recognition of the first symptom to diagnosis, were examined. Health information literacy was measured using four dimensions: cognition, search, evaluation, and application. Results: The average time from the first symptom to first medical consultation was 4.8 months, and that from the first symptom to diagnosis was 10.8 months. There is a significant delay from the onset of the initial symptoms to a definitive diagnosis. Thirty-five (24%) patients had poor while 26 (18%) had high health information literacy. The overall score for health information literacy was 69; the scores for health information cognition and application were 90 and 84, respectively. The scores for evaluation (61) and search (57) were low. Medical personnel were considered the most professional and credible sources of information. Additionally, search engines and patient organizations were the other two most important sources of health literacy. Conclusion: Patients with SMA and their caregivers had low levels of health information literacy. SMA information visibility and standardization need to be improved. Medical personnel with experience in the diagnosis and treatment of SMA and media should aim to share knowledge and increase the quality of life of those with SMA. [ABSTRACT FROM AUTHOR]

Background: Spinal muscular atrophy (SMA) is a neurodegenerative disorder. Although prior studies have investigated the metabolomes of SMA in various contexts, there is a gap in research on cerebrospinal fluid (CSF) metabolomics compared to healthy controls. CSF metabolomics can provide insights into central nervous system function and patient outcomes. This study aims to investigate CSF metabolite profiles in untreated SMA patients to enhance our understanding of SMA metabolic dysregulation. Methods: This case control study included 15 SMA patients and 14 control subjects. CSF samples were collected, and untargeted metabolomics was conducted to detect metabolites in SMA and control groups. Results: A total of 118 metabolites abundance were significantly changed between the SMA and control groups. Of those, 27 metabolites with variable importance for the projection (VIP) ≥ 1.5 were identified. The top 5 differential metabolites were N-acetylneuraminic acid (VIP = 2.38, Fold change = 0.43, P = 5.49 × 10–5), 2,3-dihydroxyindole (VIP = 2.33, Fold change = 0.39, P = 1.81 × 10–4), lumichrome (VIP = 2.30, Fold change = 0.48, P = 7.90 × 10–5), arachidic acid (VIP = 2.23, Fold change = 10.79, P = 6.50 × 10–6), and 10-hydroxydecanoic acid (VIP = 2.23, Fold change = 0.60, P = 1.44 × 10–4). Cluster analysis demonstrated that the differentially metabolites predominantly clustered within two main categories: protein and amino acid metabolism, and lipid metabolism. Conclusions: The findings highlight the complexity of SMA, with widespread effects on multiple metabolic pathways, particularly in amino acid and lipid metabolism. N-acetylneuraminic acid may be a potential treatment for functional improvement in SMA. The exact mechanisms and potential therapeutic targets associated with metabolic dysregulation in SMA require further investigation. [ABSTRACT FROM AUTHOR]

Background: The management of Spinal Muscular Atrophy (SMA) requires a multidisciplinary treatment approach, wherein rehabilitation constitutes an integral element. In this study, we examined the effects of rehabilitation among Chinese SMA patients and assessed the real-world efficacy of rehabilitation interventions. Methods: We conducted a cross-sectional online survey on SMA patients from June 9, 2023, to June 30, 2023, through the Meier Advocacy & Support Center using data from the Center's database and electronic questionnaires. The rehabilitation situation of the participants over the past 14 months were investigated. Logistic binary regression was used to analyze the relationship between Pediatric Quality of Life Inventory(PedsQL™) scores and rehabilitation. Result: A total of 186 questionnaires were finally analyzed. Only 29 patients did not rehabilitated in the past 14 months. A significant correlation between age and type of rehabilitation, as well as between age and duration of rehabilitation. Patients receiving no rehabilitation or solely home-based rehabilitation exhibited a higher median age of 8.4 compared to those undergoing standard rehabilitation or a combination of standard and home-based rehabilitation, with a median age of 4.9 (z-score = -4.49, p-value < 0.001). In addition, long-term rehabilitation (OR = 0.314, 95%CI = 0.106–0.927, p = 0.04) were negatively correlated with lower PedsQL™ Neuromuscular Module scores, and PedsQL scores in the long-term rehabilitation group were higher than those in the short-term and no-rehabilitation groups (54.2 ± 15.1 vs. 45.9 ± 14.4 and 42.3 ± 14.3, p = 0.01), with the most significant difference observed in the physical function section (59.0 ± 15.8 vs. 46.8 ± 15.2 and 45.6 ± 15.9, p < 0.01). Mobility and exercise (OR = 0.26, 95%CI = 0.08–0.81, p = 0.02), as well as assistive technology (OR = 0.28, 95%CI = 0.10–0.82, p = 0.02), were independently associated with a lower score in a negative direction. Conclusion: The study found that long-term rehabilitation was linked to higher PedsQL scores in SMA patients, highlighting the need for standardized rehabilitation programs to enhance function and quality of life. [ABSTRACT FROM AUTHOR]

Background: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China. Methods: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date. Results: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full. Conclusions: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing. [ABSTRACT FROM AUTHOR]

Background: To explore the clinical application value of pre‐conception expanded carrier screening (PECS) in the Chinese Han ethnicity population of childbearing age. Methods: The results of genetic testing of infertile parents who underwent PECS in the Reproductive Medicine Center of the Second Affiliated Hospital of Zhengzhou University, China, from September 2019 to December 2021, were retrospectively analyzed. The carrier rate of single gene disease, the detection rate of high‐risk parents, and the clinical outcome of high‐risk parents were statistically analyzed. Results: A total of 1372 Chinese Han ethnicity patients underwent PECS, among which 458 patients underwent the extended 108‐gene test, their overall carrier rate was 31.7%, and the detection rate of high‐risk parents was 0.3%. The highest carrier rates were SLC22A (2.4%), ATP7B (2.4%), MMACHC (2.2%), PAH (1.8%), GALC (1.8%), MLC1 (1.3%), UNC13D (1.1%), CAPN3 (1.1%), and PKHD1 (1.1%). There were 488 women with fragile X syndrome—FMR1 gene detection, and 6 patients (1.2%) had FMR1 gene mutation. A total of 426 patients were screened for spinal muscular atrophy—SMN1, and the carrier rate was 3.5%, and the detection rate of parents' co‐carrier was 0.5%. Conclusion: Monogenic recessive hereditary diseases had a high carrier rate in the population. Pre‐pregnancy screening could provide good prenatal and postnatal care guidance for patients and preimplantation genetic testing for monogenic/single gene disorders (PGT‐M) and prenatal diagnosis could provide more precise reproductive choices for high‐risk parents. [ABSTRACT FROM AUTHOR]

Objective: Spinal muscular atrophy (SMA) is an autosomal recessive disorder mainly affecting the neuromuscular system, which seriously threatens the life and health of patients. But few studies have reported the acceptance rate of SMA gene screening and SMA carrier rate in China. The present study aimed to clarify the two issues in China through a retrospective analysis of 18,818 reproductive age women in Wuhan area of China. Methods: The copy number (CN) of exons 7 and 8 in survival motor neuron 1 (SMN1) gene was detected by real-time quantitative PCR, and the results were verified by multiplex ligation-dependent probe amplification. Results: Carrier screening was offered to 44,953 women of childbearing age in our medical center from March, 2018, to February, 2022, of whom 18,818 were enrolled in the program. A total of 336 women were identified as carriers (1.73%; 326/18,808; without fertility history of the children with SMA). Among 18,818 reproductive age women, 286 spouses (85.12%; 286/336) were successfully recalled for screening. The results showed 17 couples at high risk of having children with SMA, of whom prenatal diagnosis was implemented in 11, and 6 fetuses were identified with SMA. All the 5 pregnant women bearing the 6 SMA fetuses chose to terminate the pregnancy by artificial abortion. Conclusion: Reproductive age women and their spouses in Wuhan area showed a positive attitude toward general screening for SMA carriers. Given the high early mortality of children with SMA, screening for SMA carriers in women of reproductive age is necessary and feasible. [ABSTRACT FROM AUTHOR]

• Patients with orphan disease were easily overlooked during the COVID-19 pandemic. • We investigated the challenges of patients with spinal muscular atrophy. • The hospitalization and intensive care unit stay rate were significantly higher in type I patients. • This is the first large evidence-based survey on patients with spinal muscular atrophy in this context. To investigate the challenges of patients with spinal muscular atrophy (SMA) during the Omicron variant COVID-19 pandemic. A cross-sectional survey was conducted in China from January 02, 2023, to January 12, 2023, using a questionnaire that covered three aspects: (1) Demographic information; (2) SMA-related information; and (3) COVID-19-related information. We recruited patients with SMA from 33 provinces. The prevalence, course, and clinical manifestations of COVID-19 were calculated. The relationships between independent and outcome variables were investigated. In total, 677 patients (male: 349; female: 328) were included in this study (average age = 11.40 years); 534 (78.88%) suffered from COVID-19. The most common symptoms were fever (95.51%), cough (57.87%), and sputum (49.44%). Of the infected patients, 91.57% recovered with at-home care, and 8.43% were hospitalized; 1.31% were admitted to the intensive care unit (ICU). A positive correlation was observed between the SMA severity and hospitalization rate. The ICU stay rate in patients with SMA type I was significantly higher than that in other SMA types. This is the first large sample survey to timely reveal the living situation of patients with SMA during the COVID-19 pandemic's Omicron variant. Patients with SMA type I should be paid more attention in terms of hospitalization and ICU stay. [ABSTRACT FROM AUTHOR]

Background: Spinal muscular atrophy (SMA) is a progressive degenerative neuromuscular disease. Nusinersen, with its quick onset of action, can benefit patients early in the treatment course. However, there are currently no clinical studies regarding the improvement in motor function and nutritional status of patients after loading period treatment with nusinersen. Here, we aimed to determine the efficacy of nusinersen in improving motor function and nutritional status in children with SMA treated with nusinersen after loading period in Western China. Methods: In this retrospective study, data for all pediatric patients (aged < 18 years), with genetically confirmed diagnosis of SMA who were treated with nusinersen, were collected before initiation of treatment and after 2 months of treatment. We assessed motor function using standardized scales and nutritional status of patients with SMA as well as side effects of nusinersen. Results: Forty-six pediatric patients aged < 18 years were enrolled in this study. After 2 months of treatment, the motor function of patients with SMA type 1, 2, and 3 improved. The difference in Revised Upper Limb Module scores from M0 to M2 was significant in patients with SMA type 2 and 3 (P = 0.004, P = 0.042, respectively). The difference in Hammersmith Functional Motor Scale Expanded scores from M0 to M2 in patients with SMA type 2 was also significant (P = 0.000). No significant differences were found for Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorder (CHOP-INTEND), Hammersmith Infant Neurologic Examination-Part 2 (HINE-2), and 6-Minute Walking Test (6MWT) scores between M0 and M2, but the scores of CHOP-INTEND, HINE-2, and 6MWT were all increased after loading period treatment. The overall improvement in nutritional status was not statistically significant. No serious adverse effects were observed. Conclusions: Our study provides evidence for the efficacy and safety of nusinersen and the nutritional status of pediatric patients with SMA after the loading period treatment. Motor function of all patients improved after 2 months of loading period nusinersen treatment. Patients with a shorter disease duration showed better response to treatment. Careful surveillance of nutritional status is needed in patients with SMA. [ABSTRACT FROM AUTHOR]

Purpose: To report the clinical characteristics and surgical outcomes of scoliosis in patients with spinal muscular atrophy (SMA) from Mainland China. Methods: Nineteen patients were retrospectively analyzed. Demographic, anthropometric and respiratory parameters were collected preoperatively. Surgical program was analyzed. Radiographic data were measured perioperatively. Motor status, ventilation support, sitting ability and respiratory symptoms were evaluated preoperatively and at final follow-up. Results: Age at surgery was 17.08 (12.83, 20.08) years. More than 40% of patients were diagnosed with low weight. Pulmonary dysfunction was observed in all patients. All patients received posterior spinal fusion (PSF). Sacroiliac fixation with sacral-2 alar iliac technique was used in 16 patients. Major curve correction rate was 54.87 ± 16.14%. Pelvic obliquity correction rate was 63.84 ± 23.70%. T1–T12 height, space-available-for-lung ratio and thoracic transverse diameter were increased (p < 0.001). Percentage of patients capable of sitting independently increased from 26.32% preoperatively to 73.68% at final follow-up. Cumulative scores of sitting-related items in muscular dystrophy spine questionnaire improved from 19.11 ± 5.40 preoperatively to 26.21 ± 5.20 at final follow-up. Total scores of symptomatic domains in St. George's Respiratory Questionnaire decreased from 4 (2, 12) preoperatively to 1 (0, 3) at final follow-up. Conclusions: SMA patients in China always present severe scoliosis at late adolescence, accompanied with high proportion of low weight and pulmonary dysfunction. PSF is effective for the correction of scoliosis and pelvic obliquity and the improvement of thoracic morphology. Sitting ability and respiratory symptoms were improved postoperatively. [ABSTRACT FROM AUTHOR]

Background: Patients with spinal muscular atrophy (SMA) may suffer from multisystem injury, including an impaired cardiovascular system. However, M-mode echocardiography, the current dominant echocardiographic modality, is limited in the detection of myocardial injury. We considered the use of left ventricular strain imaging in detecting myocardial injury and explored the serum lipid profile related to cardiovascular disease in later-onset SMA children. Methods: A case-control study involving 80 patients with later-onset SMA and 80 age-, gender-, and body surface area-matched control children was conducted in a single tertiary pediatric hospital in China. Data on the left ventricular strain measured using two-dimensional speckle tracking echocardiography, left ventricular function parameters assessed by M-mode echocardiography, and serum lipid profile of these two groups were retrospectively collected for differential analysis. Results: The mean age of the 80 SMA patients were (6.87 ± 2.87) years, of which 46 were type 2 and 34 were type 3 patients. The global longitudinal strain (GLS) of the SMA group (-18.7 ± 2.9%, p < 0.001) was lower than that of the control group; the time to peak longitudinal strain (TTPLS) of the SMA group (22.9 ± 13.6 ms, p < 0.001) was higher than that of the control group, while left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), measured by the Teichholz method of M-mode echocardiography, showed no significant differences between the two groups. In addition, independent indicators for cardiovascular risk, including total cholesterol (TC)/HDL, low-density lipoprotein (LDL)/HDL, and Apo B/Apo A1 levels, were higher in SMA children than in the control group. Conclusion: Compared with healthy controls, later-onset SMA children presented with reduced GLS and prolonged TTPLS while the LVEF and LVFS values were within normal range. In particular, whether a reduced GLS or prolonged TTPLS in later-onset SMA compared to the control group can predict the risk of future cardiomyopathy remains to be investigated. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA) is an autosomal recessive disorder with an incidence of 1/6,000-1/10,000 and is the leading fatal disease among infants. Previously, there was no effective treatment for SMA. The first effective drug, nusinersen, was approved by the US FDA in December 2016, providing hope to SMA patients worldwide. The drug was introduced in the European Union in 2017 and China in 2019 and has so far saved the lives of several patients in most parts of the world. Nusinersen are fixed sequence antisense oligonucleotides with special chemical modifications. The development of nusinersen progressed through major scientific discoveries in medicine, genetics, biology, and other disciplines, wherein several scientists have made substantial contributions. In this article, we will briefly describe the pathogenesis and therapeutic strategies of SMA, summarize the timeline of important scientific findings during the development of nusinersen in a detailed, scientific, and objective manner, and finally discuss the implications of the development of nusinersen for SMA research. [ABSTRACT FROM AUTHOR]

Objectives: The beneficial effects of many substances have been discovered because of regular dietary consumption. This is also the case with curcumin, whose effects have been known for more than 4,000 years in Eastern countries such as China and India. A curcumin-rich diet has been known to counteract many human diseases, including cancer and diabetes, and has been shown to reduce inflammation. The effect of a curcumin treatment for neurological diseases, such as spinal muscular atrophy; Alzheimer's disease; Parkinson's disease; amyotrophic lateral sclerosis; multiple sclerosis; and others, has only recently been brought to the attention of researchers and the wider population. Methods: In this paper, we summarise the studies on this natural product, from its isolation two centuries ago to its characterisation a century later. Results: We describe its role in the treatment of neurological diseases, including its cellular and common molecular mechanisms, and we report on the clinical trials of curcumin with healthy people and patients. Discussion: Commenting on the different approaches adopted by the efforts made to increase its bioavailability. [ABSTRACT FROM AUTHOR]

Background and Aims: Both Charcot‐Marie‐Tooth disease type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA‐V) are GARS1 disease phenotypes involving axonal peripheral neuropathy. Patients often develop clinical symptoms in their teens. Herein, we reported a Chinese family with infantile‐onset CMT2D/dSMA‐V. Methods: Clinical evaluation and laboratory examination were performed in our proband, the older sister from this family, and trio exome sequencing (ES) was conducted on the proband and her parents, followed by Sanger sequencing. Results: A novel GARS1 mutation (c.997G>C, p.E333Q; NM_002047) was identified in this patient and her younger sister but not in her parents; thus, it is presumed that this mutation is inherited from a germline mosaic parent. The younger sister began to exhibit weakness of her hands and feet at the age of 1 year old. Conclusion: This is the first report of infantile CMT2D/dSMA‐V in China. Our study increases the number of infantile‐onset cases, as well as reported pathogenic variants in the GARS1 gene, and highlights the important role of exome sequencing in the clinical diagnosis of disease and enabling subsequent prenatal diagnosis. Our study reminds us to consider the possibility of parent germline mosaicism in the subsequent prenatal genetic diagnosis when identifying a de novo variant. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness and safety of nusinersen for the treatment of 5q-spinal muscular atrophy (SMA) among Chinese pediatric patients., Methods: Using a longitudinal, multi-center registry, both prospective and retrospective data were collected from pediatric patients with 5q-SMA receiving nusinersen treatment across 18 centers in China. All patients fulfilling the eligibility criteria were included consecutively. Motor function outcomes were assessed post-treatment by SMA type. Safety profile was evaluated among patients starting nusinersen treatment post-enrollment. Descriptive analyses were used to report baseline characteristics, effectiveness, and safety results., Results: As of March 2nd, 2023, 385 patients were included. Most patients demonstrated improvements or stability in motor function across all SMA types. Type II patients demonstrated mean changes [95% confidence interval (CI)] of 4.4 (3.4-5.4) and 4.1 (2.8-5.4) in Hammersmith Functional Motor Scale-Expanded (HFMSE), and 2.4 (1.7-3.1) and 2.3 (1.2-3.4) in Revised Upper Limb Module (RULM) scores at months 6 and 10. Type III patients exhibited mean changes (95% CI) of 3.9 (2.5-5.3) and 4.3 (2.6-6.0) in HFMSE, and 2.1 (1.2-3.0) and 1.5 (0.0-3.0) in RULM scores at months 6 and 10. Of the 132 patients, 62.9% experienced adverse events (AEs). Two patients experienced mild AEs (aseptic meningitis and myalgia) considered to be related to nusinersen by the investigator, with no sequelae., Conclusions: These data underscore the significance of nusinersen in Chinese pediatric patients with SMA regarding motor function improvement or stability, and support recommendations on nusinersen treatment by Chinese SMA guidelines and continuous coverage of nusinersen by basic medical insurance., (© 2024. The Author(s).)

Introduction: Spinal muscular atrophy (SMA) is a rare, autosomal recessive, neuromuscular disease that leads to progressive muscular weakness and atrophy. Nusinersen, an antisense oligonucleotide, was approved for SMA in China in February 2019. We report interim results from a post-marketing surveillance phase 4 study, PANDA (NCT04419233), that collects data on the safety, efficacy, and pharmacokinetics of nusinersen in children with SMA in routine clinical practice in China., Methods: Participants enrolled in PANDA will be observed for 2 years following nusinersen treatment initiation. The primary endpoint is the incidence of adverse events (AEs)/serious AEs (SAEs) during the treatment period. Efficacy assessments include World Health Organization (WHO) Motor Milestones assessment, the Hammersmith Infant Neurological Examination (HINE), and ventilation support. Plasma and cerebrospinal fluid (CSF) concentrations of nusinersen are measured at each dose visit., Results: Fifty participants were enrolled as of the January 4, 2023, data cutoff: 10 with infantile-onset (≤ 6 months) and 40 with later-onset (> 6 months) SMA. All 50 participants have received at least one dose of nusinersen; 6 have completed the study. AEs were experienced by 45 (90%) participants and were mostly mild/moderate; no AEs led to nusinersen discontinuation or study withdrawal. Eleven participants experienced SAEs, most commonly pneumonia (n = 9); none were considered related to study treatment. Stability or gain of WHO motor milestone was observed and mean HINE-2 scores improved in both subgroups throughout the study. No serious respiratory events occurred, and no permanent ventilation support was initiated during the study. Pre-dose nusinersen CSF concentrations increased steadily through the loading-dose period, with no accumulation in plasma after multiple doses., Conclusion: Nusinersen was generally well tolerated with an acceptable overall safety profile, consistent with the known safety of nusinersen. Efficacy, safety, and nusinersen exposure are consistent with prior observations. These results support continuing PANDA and evaluation of nusinersen in Chinese participants with SMA., Trial Registration: ClinicalTrials.gov identifier, NCT04419233., (© 2024. The Author(s).)

Objective: The objective of this study was to examine the psychometric properties of the EQ-5D-Y-3 L, Patient Reported Outcomes Measurement System 25-item version profile v2.0 (PROMIS-25), and Pediatric Quality of Life Inventory™ version 4.0 Generic Core Scale (PedsQL 4.0) in Chinese pediatric patients with spinal muscular atrophy (SMA)., Methods: The data used in this study were obtained via a web-based cross-sectional survey. Parents of pediatric patients with SMA completed the proxy-reported EQ-5D-Y-3 L, PedsQL 4.0, and PROMIS-25 measures. Information about socioeconomic and health status was also obtained. The ceiling and floor effects, factorial structure, convergent validity, and known-group validity of the three measures were assessed., Results: Three hundred and sixty-three parents of children aged from 5 to 12 completed the questionnaires. Strong floor effects were observed for the physical function components of the PROMIS-25 (41.3%) and PedsQL 4.0 (67.8%). For EQ-5D-Y-3 L, 84.6% of the respondents reported having "a lot of" problems with the dimensions "walking" and "looking after myself." Minimal ceiling or floor effects were observed for the EQ-5D-Y-3 L index value. The confirmatory factor analysis supported a six-factor structure for the PROMIS-25, but did not support a four-factor structure for the PedsQL 4.0. All hypothesized correlations of the dimensions among the three measures were confirmed, with coefficients ranging from 0.28 to 0.68. Analysis of variance showed that EQ-5D-Y-3 L demonstrated better known-group validity than the other two measures in 14 out of 16 comparisons., Conclusions: The EQ-5D-Y-3 L showed better discriminant power than the other two measures. The physical health dimensions of all three measures showed the significant floor effects. These findings provide valuable insights into the effectiveness of these measures at capturing and quantifying the impact of SMA on patients' health-related quality of life., (© 2024. The Author(s).)

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Background: Spinal muscular atrophy (SMA) is a rare neurogenetic disease which involves multisystem dysfunctions such as respiratory, digestive, and motor disorders. Anxiety, depression and other psychological disorders often accompany severe chronic physical diseases. The aim of this study was to investigate the prevalence of anxiety and depression along with their influencing factors among school-age patients with SMA.Methods: We conducted a cross-sectional study on school-age SMA patients in China. Patients aged 8-18 years with a genetic diagnosis of 5qSMA were invited to answer a questionnaire composed of sociodemographic and clinical questions, then to complete the Screen for Child Anxiety-Related Emotional Disorders and Depression Self-Rating Scale for depression and anxiety level evaluation. At the end of the questionnaire, further questions assessed the subjective anxiety and subjective depression of patients' caregivers and their expectations for their child's future.Results: Complete data were available for 155 patients. The sample included 45.8% boys and 54.2% girls; 65.2% were type II, 27.1% were type III, and the remainder were type I SMA. Rates of anxiety and depression in these school-age SMA patients were 40.0% and 25.2%, respectively. Gender, age, and disease type were not associated with anxiety or depression, but respiratory system dysfunction, digestive system dysfunction, skeletal deformity, rehabilitation exercise, academic delay, specialized support from school, household income level, caregivers' subjective anxiety, and caregivers' expectations were significantly related to both anxiety and depression.Conclusions: There was a high prevalence of anxiety and depression in school-age SMA patients in China. Professional psychological care maybe included in the standard of care. These results also call for possible targets for intervention such as reducing complications, improving drug accessibility, retaining normal schooling, strengthening school support, and enhancing the ability of the caregivers of SMA patients to assist in the diagnosis and treatment of the disease, so improving the mental health of SMA patients. [ABSTRACT FROM AUTHOR]

Background: Patients with spinal muscular atrophy (SMA) are at risk of decreased bone mineral density (BMD). The bone health status of Chinese patients with SMA has been poorly studied. We aimed to evaluate the BMD of children with SMA types 2 and 3 in mainland China and investigate its influencing factors.Methods: Forty patients with a mean age of 5.5 years affected by SMA types 2 and 3 (n = 22 and n = 18, respectively) were enrolled between September 2017 and May 2019. Total body less head (TBLH) BMD, lumbar spine (LS) BMD, and body composition were measured using dual-energy X-ray absorptiometry (DXA). Serum bone metabolism markers and complete spinal radiographs were assessed. We utilized a linear regression model to explore the correlations between BMD and its related factors.Results: A total of 67.5% (27/40) of patients were diagnosed with low BMD and 2.5% (1/40) were diagnosed with osteoporosis. The TBLH BMD and LS BMD Z-scores in children with SMA type 2 were significantly lower than those with SMA type 3. Both TBLH and LS BMD Z-scores tended to increase with the change of SMA subtypes from 2a-3b. Vitamin D insufficiency and deficiency were found in 37.5% (15/40) of the patients. Serum Ca, phosphorus (P), alkaline phosphatase (ALP) and parathormone (PTH) levels were normal. There were no significant differences among the four subtypes in terms of all the serum bone metabolism markers. Phenotype was significantly associated with TBLH BMD and LS BMD Z-scores, and serum PTH levels were significantly associated with TBLH BMD Z-scores.Conclusions: Low BMD and osteoporosis were highly prevalent in mainland Chinese children with SMA types 2 and 3. Phenotype and serum PTH level might be the influencing factors of BMD. Regular monitoring of BMD by DXA scan and taking active interventions aim to SMA children with different types are important. [ABSTRACT FROM AUTHOR]

• Delayed diagnosis is common in spinal muscular atrophy (SMA). • Type I/II SMA patients visited about 2.56 doctors before obtaining an SMA diagnosis. • Type III SMA patients visited about 3.94 doctors before obtaining an SMA diagnosis. • A national register for rare diseases could enhance identification of SMA. • Collaboration networks and neonatal screening could also reduce diagnostic delays. Spinal muscular atrophy (SMA) is a rare neuromuscular disease, which often occurs in childhood. Early SMA treatment may be highly beneficial to SMA patients, their families, and society. However, delayed diagnosis is common. To identify the factors that affect the SMA diagnostic time window, we analyzed disease characteristics, family factors, and medical factors of 205 SMA families. We compared the data with those of our previous cohort to explore the dynamic changes in the diagnostic time window. The median diagnostic time windows for SMA types I, II, and III were 3.38 [interquartile range (IQR): 2.01–4.98], 4.08 (IQR: 2.07–8.17), and 11.37 (IQR: 4.92–24.07) months, respectively. The diagnostic time window in patients who were clinically diagnosed with SMA at their first hospital visit was 49.42% shorter than that in other patients. Type I/II patients visited approximately 2.56 doctors before diagnosis, while type III patients visited approximately 3.94 doctors before diagnosis. The diagnostic time windows for types II and III were 54.67 and 62.10% shorter, respectively, than those in the previous cohort, which is mainly due to improvements in medical capacity. Therefore, with public awareness, increased medical personnel understanding, and increased neonatal screening, the SMA diagnostic time window is expected to further reduce. [ABSTRACT FROM AUTHOR]

Heterozygous carriers of the survival of motor neuron 1 (SMN1) gene deletion in parents account for approximately 95% of neonatal spinal muscular atrophy cases. Given the severity of the disease, professional organizations have recommended periconceptional spinal muscular atrophy carrier screening to all couples, regardless of race or ethnicity. However, the prevalence of screening activities in mainland China remains suboptimal, mainly attributed to the limitations of the existing carrier screening methods. Herein, we aimed to develop a low-cost, accessible, and accurate carrier screening method based on duplex droplet digital PCR (ddPCR), to cover a wider population in developing countries, including China. The receiver operating characteristic curve was used to determine the cut-off value of SMN1 copy numbers. Performance validation was conducted for linearity, precision, and accuracy. In total, 482 cases were considered to validate the concordance between the developed ddPCR assay and multiplex ligation-dependent probe amplification. Linear correlations were excellent between the expected concentration of the reference gene and the observed values (R2 > 0.99). Both the intra- and inter-assay precision of our ddPCR assays were less than 6.0%. The multiplex ligation-dependent probe amplification and ddPCR results were consistent in 480 of the 482 cases (99.6%). Two cases with multiplex ligation-dependent probe amplification, suggestive of two copies of SMN1 exon 7, were classified into three copies by ddPCR analysis. The overall correct classification of the samples included in our ddPCR assay was 100%. This study demonstrates that an appropriate cut-off value is an important prerequisite for establishing a semi-quantitative method to determine the SMN1 copy numbers. Compared to conventional methods, our ddPCR assay is low-cost, highly accurate, and has full potential for application in population spinal muscular atrophy carriers screening. • Spinal muscular atrophy (SMA) is a common lethal monogenetic disorder. • A ddPCR assay for determining SMN1 copy numbers was developed. • The assay improved the accessibility and reproducibility of SMA carrier screening. • The developed ddPCR assay has the advantages of rapidity, high accuracy, and affordability. [ABSTRACT FROM AUTHOR]

Background: Spinal muscular atrophy (SMA) is an autosomal-recessive motor neuron disease leading to dysfunction of multiple organs. SMA can impair the quality of life (QoL) of patients and family. We aimed to evaluate the QoL of children with SMA and their caregivers and to identify the factors associated with QoL in a cross-sectional study conducted in China.Methods: We recruited 101 children aged 0-17 years with SMA and their caregivers from a children's hospital in China. Twenty-six children had type I SMA, 56 type II and 19 type III. Each child's QoL was measured by the Pediatric Quality of Life Inventory 3.0 Neuromuscular Module (PedsQL NMM), which was completed by the child's caregivers. The caregiver's QoL was measured by the Pediatric Quality of Life Inventory Family Impact Module (PedsQL FIM). Information on sociodemographic characteristics, disease-specific characteristics, and treatments were collected using the proxy-reported questionnaire. Two-sample t tests and one-way ANOVA were used to compare differences in average scores of QoL across subgroups.Results: Children with type III SMA had a higher average Total score of PedsQL NMM and higher average scores in domains Neuromuscular disease and Family resources than children with type I or type II SMA (p < 0.001). Caregivers of children with type III SMA reported higher average scores in the domains of Physical, Emotional, Social, and Cognitive functioning of the PedsQL FIM than those of children with types I or II SMA (p < 0.05). In addition, disease-related characteristics (e.g. limited mobility, stable course of disease, skeleton deformity, and digestive system dysfunction) and respiratory support were associated with lower average scores of PedsQL NMM and PedsQL FIM (p < 0.05). Exercise training, multidisciplinary team management and use of the medication Nusinersen were each associated with higher average scores in both PedsQL NMM and FIM (p < 0.05).Conclusion: Our study has demonstrated factors that may impair or improve QoL of children patients with SMA and their parents. Particularly, QoL was relatively poor in children with type I and type II SMA as well as in their caregivers compared to those with type III SMA. We strongly recommend that standard of care in a multidisciplinary team be strengthened to improve the QoL of SMA patients. Our study called for increased attention from clinical physicians on measuring QoL in their clinical practices in order to enhance the understanding of impacts of SMA and to make better decisions regarding treatment. [ABSTRACT FROM AUTHOR]

Background: Spinal muscular atrophy (SMA) is a common and lethal autosomal recessive neurodegenerative disease caused by mutations in the survival motor neuron 1 (SMN1) gene. At present, gene therapy medicine for SMA, i.e., Spinraza (Nusinersen), has been approved by the FDA, bringing hope to SMA patients and families. Accurate diagnosis is essential for treatment. Our goal was to detect genetic mutations in SMA patients in China and to show the results of the prenatal diagnosis of SMA. Methods: In this study, we examined 419 patients in our hospital from January 2010 to September 2019. Multiplex ligation-dependent probe amplification analysis was used to determine the copy numbers of SMN1 and SMN2. Long-range PCR combined with nested PCR was used to detect point mutations in SMN1. In addition to the above detection methods, we also used QF-PCR in prenatal diagnosis to reduce the impact of maternal contamination. We conducted a total of 339 prenatal diagnoses from January 2010 to September 2019. Results: Homozygous deletion of SMN1 exon 7 was detected in 96.40% (404/419) of patients. Homozygous deletion of SMN1 exon 7 alone was detected in 15 patients (3.60%). In total, 10 point mutations were detected in the 15 pedigrees. Most patients with SMA Type I have 1 ~ 2 copies of the SMN2 gene. Patients with SMA Type II have 2 or 3 copies of the SMN2 gene. The results of prenatal diagnoses showed that 118 fetuses were normal, 149 fetuses were carriers of heterozygous variants, and the remaining 72 fetuses harbored compound heterozygous variants or homozygous variants. Conclusions: Our study found that the most common mutation in SMA was homozygous deletion of SMN1 exon 7 in our study. We suggest that detecting only the deletion of exon 7 of SMN1 can meet most of the screening needs. We also believe that SMN2 copy numbers can help infer the disease classification and provide some reference for future treatment options. [ABSTRACT FROM AUTHOR]

• Novel mutations identified in this study enriched the SMN1 mutation database. • Revealing a distinct ethnic specificity in the SMN1 mutational spectrum. • Provided a new option for the detection of Chinese common mutation c.22dupA. Spinal muscular atrophy (SMA) is caused by homozygous deletions of the SMN1 gene in approximately 95% of patients. The remaining 5% of patients with SMA retain at least one copy of the SMN1 gene carrying insertions, deletions, or point mutations. Although molecular genetic testing for most SMA patients is quite easy, diagnosing "nondeletion" SMA patients is still compromised by the presence of a highly homologous SMN2 gene. In this study, we analyzed the SMN1/SMN2 copy number by quantitative PCR and multiplex ligation-dependent probe amplification (MLPA). Further, common primers for both SMN1 and SMN2 sequences were used to screen DNA intragenic mutations. To confirm whether the identified mutations occurred in SMN1 or SMN2 , we improved the traditional RT-PCR method by only amplifying SMN1 transcripts using an allelic-specific PCR (AS-RT-PCR) strategy. We identified six SMN1 point mutations and small indels in 8 families, which included c.683T>A, c.22dupA, c.815A>G, c.19delG, c.551_552insA and c.401_402delAG. To the best of our knowledge, the latter three have never been previously reported. The most common mutation in Chinese patients is c.22dupA, which was identified in three families. In this work, we demonstrated AS-RT-PCR to be reliable for identifying SMN1 subtle mutations, especially the prevalent mutation c.22dupA in Chinese SMA patients. By reviewing published papers and summarizing reported SMN1 mutations, a distinct ethnic specificity was found in SMA patients from China. Our research extends the SMN1 mutation spectrum. [ABSTRACT FROM AUTHOR]

Background: Spinal muscular atrophy (SMA) is the most common neurodegenerative disorder and the leading genetic cause of infant mortality. Early detection of SMA through newborn screening (NBS) is essential to selecting pre-symptomatic treatment and ensuring optimal outcome, as well as, prompting the urgent need for effective screening methods. This study aimed to determine the feasibility of applying an Agena iPLEX SMA assay in NBS for SMA in China. Methods: We developed an Agena iPLEX SMA assay based on the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and evaluated the performance of this assay through assessment of 167 previously-genotyped samples. Then we conducted a pilot study to apply this assay for SMA NBS. The SMN1 and SMN2 copy number of screen-positive patients were determined by multiplex ligation-dependent probe amplification analysis. Results: The sensitivity and specificity of the Agena iPLEX SMA assay were both 100%. Three patients with homozygous SMN1 deletion were successfully identified and conformed by multiplex ligation-dependent probe amplification analysis. Two patients had two SMN2 copies, which was correlated with severe SMA type I phenotype; both of them exhibited neurogenic lesion and with decreased muscle power. Another patient with four SMN2 copies, whose genotype correlated with milder SMA type III or IV phenotype, had normal growth and development without clinical symptoms. Conclusions: The Agena iPLEX SMA assay is an effective and reliable approach for population-based SMA NBS. The first large-scale pilot study using this assay in the Mainland of China showed that large-scale implementation of population-based NBS for SMA is feasible. [ABSTRACT FROM AUTHOR]

Background: To determine the carrier frequency of, and evaluate a carrier screening program for, spinal muscular atrophy (SMA) in reproductive age women in Shenzhen area., Methods: A staged screening procedure was used to perform carrier screening for SMA in 22,913 Chinese reproductive age women between 2019 and 2022 in Shenzhen area of China. First, the copy number of exon 7 in the SMN1 gene were detected in women of reproductive age using real-time quantitative polymerase chain reaction. If SMA carriers were detected, their spouses were then recommended to test. Prenatal diagnosis was carried out in couples who were both carriers., Results: A total of 389 women were found to be SMA carriers (1.70%, 95% CI: 1.53%-1.87%), indicating the carrier prevalence was approximately 1:59. Despite the proportion of nonpregnant women increased from 37.96% in 2019 to 58.18% in 2022 (p < 0.05) among the 22,913 reproductive age women, the recall rate of spouses was still not high (62.21%, 95% CI: 57.39%-67.03%). Eight partners were found to be SMA carriers and two fetuses were determined to have SMA with no copies of the SMN1 gene., Conclusion: Although the acceptability and awareness of SMA carrier screening in Chinese population has increased in recent years, it still fails to reach the ideal expectation. Our experience may provide a basis for and facilitate the popularization of SMA carrier screening in Shenzhen area., (© 2024 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Objective: A total of 5,200 pregnant women in Zhaoqing city, Guangdong Province, were screened to identify spinal muscular atrophy (SMA) mutation carriers to guide the prevention of SMA and prevent the birth of children with SMA., Methods: Exons 7 and 8 (E7 and E8) of the survival motor neuron (SMN) 1 gene were detected in women using real-time fluorescence quantitative polymerase chain reaction. SMN1 and SMN2 copy numbers in those who were initially identified as carriers were verified via targeted region capture and next-generation sequencing. When both partners were identified as carriers, prenatal diagnosis of the fetus was performed., Results: Among the screened women, 75 SMA carriers (71 cases had both E7 and E8 heterozygous deletions and 4 cases only had an E7 heterozygous deletion) were identified, with a carrier frequency of 1.44% (95% confidence interval: 1.31-1.65%). Three couples where both spouses were identified as SMA carriers, and their three fetuses were subjected to prenatal genetic analysis. Of the three, one had homozygous deletions of E7 and E8 and the other two had heterozygous deletions of E7 and E8. After a detailed prenatal consultation, the former couple decided to terminate the pregnancy., Conclusion: Through screening and prenatal diagnosis of pregnant women in Zhaoqing city, Guangdong Province, the incidence of SMA can be reduced, prevention of birth defects can be improved, incidence of birth defects can be effectively minimized., (© 2023. The Author(s).)

Objectives: This study aimed to evaluate the potential budget impact of nusinersen in the treatment of spinal muscular atrophy (SMA) from the perspective of the basic medical insurance payer in China., Methods: A budget impact analysis model was developed according to ISPOR budget impact analysis guidelines; we integrated health resource consumption, epidemiology, and market data for the treatment of patients with SMA in China, to estimate the impact of nusinersen on basic medical insurance. The microcosting method was conducted to evaluate the treatment cost. One-way sensitivity analysis was performed to explore the stability of the results., Results: If nusinersen could be reimbursed, the impact on the medical insurance funds in the next 1 to 3 years will be 253 million, 333 million, and 426 million, respectively. In addition, it can reduce 0.73 million, 2.17 million, and 2.22 million in complication costs, respectively., Conclusions: SMA is a rare disease with a very low prevalence; reimbursement of nusinersen will lead to a limited impact on the basic medical insurance and improve the accessibility of treatment., (Copyright © 2022 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: Spinal muscular atrophy (SMA) is the most common autosomal recessive disease in children, and the diagnosis is complicated and difficult, especially at early stage. Early diagnosis of SMA is able to improve the outcome of SMA patients. In our study, Real-time PCR was developed to measure the gene mutation or deletion of key genes for SMA and to further analyse genotype-phenotype correlation.Methods: The multiple real-time PCR for detecting the mutations of survival of motor neuron (SMN), apoptosis inhibitory protein (NAIP) and general transcription factor IIH, polypeptide 2 gene (GTF2H2) was established and confirmed by DNA sequencing and multiplex ligation-dependent probe amplification (MLPA). The diagnosis and prognosis of 141 hospitalized children, 100 normal children and further 2000 cases of dry blood spot (DBS) samples were analysed by this multiple real-time PCR.Results: The multiple real-time PCR was established and the accuracy of it to detect the mutations of SMN, NAIP and GTF2H2 was at least 98.8 % comparing with DNA sequencing and MLPA. Among 141 limb movement disorders children, 75 cases were SMA. 71 cases of SMA (94.67 %) were with SMN c.840 mutation, 9 cases (12 %) with NAIP deletion and 3 cases (4 %) with GTF2H2 deletion. The multiple real-time PCR was able to diagnose and predict the prognosis of SMA patients. Simultaneously, the real-time PCR was applied to detect trace DNA from DBS and able to make an early diagnosis of SMA.Conclusion: The clinical and molecular characteristics of SMA in Southwest of China were presented. Our work provides a novel way for detecting SMA in children by using real-time PCR and the potential usage in newborn screening for early diagnosis of SMA. [ABSTRACT FROM AUTHOR]

Introduction: Spinal muscular atrophy (SMA) is a rare autosomal-recessive neuromuscular disease. Health state utility values (HSUV) are used in health economic evaluation regarding the desirability of health outcomes such as a certain health state or change in health states over time. There is no utility data of Chinese patients with SMA., Materials and Methods: Vignettes were developed for 10 pediatric neurologists to value the utility of Chinese patients with Type I SMA. A mixed patient/proxy derived approach using EQ-5D-Y-3L, EQ-5D-3L, and CHU9D was adopted to estimate the HSUV data of patients with Type II and III SMA, including 112 patients and 301 caregivers., Result: The utility of Type I SMA patients ranged from 0.19 to 0.72 with the health state improved from "permanent ventilation" to "walking". The utility of children patients with Type II and III SMA derived from EQ-5D-Y-3L ranged from 0.33 to 0.82 while that derived from CHU9D ranged from 0.46 to 0.75. The utility of adult patients with Type II and III SMA measured by EQ-5D-3L ranged from 0.30 to 0.83., Conclusion: The better health states the patients with SMA were in, the higher were the HSUV. The utilities derived from population with different age and disease subtypes were not statistically different when patients with SMA were in the same health states. We recommend further studies on the Chinese specific value set for EQ-5D-Y-3L and other PBMs for children to derive more robust utility data., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Zhu, Bao, Liu, Xing, Kang and Jin.)

Objective: To evaluate the nutritional status of children with SMA types II and III in a Chinese population., Methods: We performed a retrospective medical record review of prospectively collected data from children with SMA types II and III in a single centre. We analysed data including clinical parameters, anthropometrics, and 24-hour dietary intake records in our clinic., Results: We analysed the anthropometric data from 86 children with 69 (80%) SMAII and 17 (20%) SMAIII; 47 (55%) were female, mean age was 5.22 ± 3.73 years. The WAZ of the SMAII ( n  = 69) and SMAIII ( n  = 17) were -0.48 (IQR -1.69, 0.57) vs -0.53 (IQR -1.60, 0.55), P  = 0.926; the HAZ were -0.62 (IQR -1.4, 0.3) vs -0.6 (IQR -1.61, 0.4), P =0.72; the BMIZ were -0.51 (IQR -1.53, 0.99) vs -0.08 (IQR -1.625, 1.125), P  = 0.537.The dietary intake of 51 children was compared to the Chinese Dietary Reference Intakes (DRIs). The actual energy intake in SMAII was similar to the DRIs, but which in SMAIII was less than the DRIs (1312.4 ± 329.5 kcal vs. 1655 ± 640.1 kcal, P  = 0.028). The protein intake in SMAII and SMAIII was higher than the DRIs (55 ± 16.3 g/d vs 30.2 ± 4.6 g/d, P  < 0.05; 56.8 ± 18.1 g/d vs 41.5 ± 17.5 g/d, p  = 0.22), and calcium intake was lower than the recommendation (507.7 ± 177.8 mg/d vs 731.7 ± 123.4 mg/d, P  < 0.05; 478.4 ± 207.4 mg/d vs 478.4 ± 207.4 mg/d, P  = 0.01). Swallowing on the Neuromuscular Disease Status Scale was 7.41 ± 0.5., Conclusions: Children with SMAII and SMAIII were at risk for malnutrition and low calcium intake.

The authors retrospectively studied the natural history of 237 patients with infantile spinal muscular atrophy in China. The onset ages (mean ± SD) for types I to III were 3.1 ± 2.7, 8.7 ± 3.8, and 21.1 ± 11.7 months, respectively. The survival probabilities for type I patients at 1, 2, and 5 years were 44.9%, 38.1%, and 29.3%, respectively, and for type II patients, the probabilities were 100%, 100%, and 97%, respectively. All type III patients were alive. Type I patients with onset age after 2 months had significantly increased survival than those with onset before 2 months (P < .05). It should be noticed that survival probability at 2 years in type I patients in our study was close to that in other Asian samples of spinal muscular atrophy, but slightly better than that among whites. Patients accepted minimal proactive interventions other than antibiotics for pulmonary infection, so our study provides reliable baseline data of natural history of spinal muscular atrophy in China. [ABSTRACT FROM AUTHOR]

Screening for carriers of spinal muscular atrophy (SMA) is necessary for effective clinical/prenatal diagnosis and genetic counseling. However, a population-based study of SMA prevalence in mainland China has not yet been conducted. In this study, the copy number of survival motor neuron (SMN) genes was determined in 1712 newborn cord blood samples collected from southern China and from 25 core families, which included 26 SMA patients and 44 parents, to identify SMA carriers. The results presented 13 groups with different SMN1/SMN2 ratios among 1712 newborn individuals, which corresponded to 1535 subjects with two copies of SMN1, 119 with three copies of SMN1, 17 with four copies of SMN1, and 41 with a heterozygous deletion of SMN1 exon 7. Simultaneously, two ‘2+0’ genotypes and two point mutations were found among the 44 obligate carriers in the core families, including a novel SMN1 splice-site mutation that was identified in the junction between intron 6 and exon 7 (c. 835–1G>A). These results indicated that the carrier frequency is 1/42 in the general Chinese population and that duplicated SMN1 alleles and de novo deletion mutations are present in a small number of SMA carriers. In addition, we developed and validated a new alternative screening method using a reverse dot blot assay for rapid genotyping of deletional SMA. Our research elucidated the genetic load and SMN gene variants that are present in the Chinese population, and could serve as the basis for a nationwide program of genetic counseling and clinical/prenatal diagnosis to prevent SMA in China. [ABSTRACT FROM AUTHOR]

Objective. Spinal muscular atrophy (SMA) is common. The prevalence of SMA in southern Chinese is 1 in 53 000. The clinical course is variable. The traditional classification of SMA includes age of onset, age of death, achievement of motor milestones, and ambulatory status as criteria. There was a lack of inclusion of the best lifetime functional status of any child with SMA. With the advances in medical care, the life expectancy and ambulatory status of patients with SMA have improved. The objective of this study was to assess the survival pattern, ambulatory status, and functional status of children with SMA. Methods. Patients with SMA were recruited from the neuromuscular clinic of the Duchess of Kent Children's Hospital, which is a university-affiliated hospital, and the Families of SMA in Hong Kong. By September 2002, 102 SMA cases had been registered in the Duchess of Kent Children's Hospital neuromuscular clinic and Families of SMA registry, and 83 patients were analyzed. Among them, 39 were recruited for the administration of Functional Independence Measure for Children (WeeFIM), an assessment tool for functional status that has been previously validated by us for Chinese children. The diagnosis of SMA was made from clinical history, serum muscle enzyme, electromyography, muscle biopsy, and, recently, by molecular studies. In Hong Kong, molecular tests of the survivor motor neuron gene was available since 1995. A total of 36 in our cohort of 83 patients had the diagnosis confirmed with molecular analyses. We adopted the classification of SMA from previous studies in which the criteria were based on the International SMA consortium (1992) with modifications according to the 59th European Neuromuscular Center International Workshops. As only SMA patients with childhood onset were studied, we did not include any type IV patients in our study. Parents were interviewed and records were reviewed for demographic... [ABSTRACT FROM AUTHOR]

Our objective was to study the prevalence of neuromuscular diseases in Chinese children. A prospective study of neuromuscular diseases in Chinese children was conducted from 1985 to 2001 in Hong Kong, which is a city in southern China. The population census of June 30, 2001, was used to calculate the prevalence of neuromuscular diseases in Chinese children. Altogether, 332 children aged < 19 years at first assessment with neuromuscular diseases confirmed by using electromyography, muscle biopsy, and/or molecular genetic study were included in the study. Of these, 228 (68%) had inherited and 104 (32%) had noninherited neuromuscular diseases. Of the inherited neuromuscular diseases, the most common were the dystrophinopathies, including Duchenne muscular dystrophy (n = 66) and Becker muscular dystrophy (n = 8). Spinal muscular atrophy was the second most common (n = 61). Of the noninherited neuromuscular disorders, myasthenia gravis was the most common (n = 62, 60%). Nearly 88% of the cases of myasthenia gravis were ocular type. The prevalence rate of neuromuscular diseases in June 2001 (n = 291 surviving) is estimated to be 214 × 10[sup−6]. The estimated prevalence rate of neuromuscular diseases in our Chinese children is 1 in 4669. (J Child Neurol 2003;18:217–219). [ABSTRACT FROM AUTHOR]

Background: Spinal muscular atrophy (SMA) is an autosomal recessive hereditary disease associated with severe muscle atrophy and weakness in the limbs and trunk. The discovery of mutated genes is helpful in diagnosis and treatment for SMA. Methods: Eighty-three whole blood samples were collected from 28 core families of clinically suspected SMA, and multiplex ligation probe amplification (MLPA) was performed. Afterwards, the complete gene sequence of SMN1 gene was detected. Furthermore, 20 SMA patients were selected from the 28 probands, and 5 non SMA children as controls. The Life Technologies SOLiD™ technology with mate-pair chemistry was utilized to conduct the whole exome high-throughput sequencing. Results: Twenty-two probands were SMA patients, 3 probands carriers, and 3 probands normal individuals. Moreover, 2 parents from 2 SMA families were with 3 SMN1 exon7 copies. Six SMN1 single nucleotide variants (SNVs) were identified in the 83 samples, and c.[84C > T], c.[271C > T], c.[−39A > G] and g.[70240639G > C] were novel. Compared with control group, 9102 mutation were selected out in SMA patients. SPTA1 mutation c.[−41_-40insCTCT], FUT5 SNV c.[1001A > G], and MCCC2 SNV c.[−117A > G] were the 3 most frequent mutations in SMA group (95, 85 and 75%, respectively). Conclusions: We identified some mutations in both SMN1 and other genes, and c.[271C > T], c.[−41_-40insCTCT], c.[1001A > G] and c.[−117A > G] might be associated with the onset of SMA. [ABSTRACT FROM AUTHOR]

Background: Charcot-Marie-Tooth (CMT) disease is an exciting field of study, with a growing number of causal genes and an expanding phenotypic spectrum. The microrchidia family CW-type zinc finger 2 gene (MORC2) was newly identified as a causative gene of CMT2Z in 2016. We aimed to describe the phenotypic-genetic spectrum of MORC2-related diseases in the Chinese population., Methods: With the use of Sanger sequencing and Next Generation Sequencing (NGS) technologies, we screened a cohort of 284 unrelated Chinese CMT2 families. Pathogenicity assessments of MORC2 variants were interpreted according to the ACMG guidelines. Potential pathogenic variants were confirmed by Sanger sequencing., Results: We identified 4 different heterozygous MORC2 mutations in four unrelated families, accounting for 1.4% (4/284). A novel mutation c.1397A>G p. D466G was detected in family 1 and all affected patients presented with later onset axonal CMT with hyperCKemia. The patient in family 2 showed a spinal muscular atrophy (SMA)-like disease with cerebellar hypoplasia and mental retardation, with a hot spot de novo mutation c.260C>T p. S87L. The twin sisters in family 3 were identified as having the most common mutation c.754C>T p. R252W and suffered from axonal motor neuropathy with high variability in disease severity and duration. The patient in family 4 developed an early onset axonal motor and sensory neuropathy, with a reported mutation c.1220G>A p.C407Y. All identified mutations associated with MORC2-related neuropathies are localized in the N-terminal ATPase module., Conclusions: Our study confirmed that MORC2-related neuropathies exist in the Chinese population at a relatively high mutation rate. We revealed a complex genotype-phenotype correlation with MORC2 mutations. This report adds a new piece to the puzzle of the genetics of CMT and contributes to a better understanding of the disease mechanisms.

We evaluated survival motor neuron 2 (SMN2) and neuronal apoptosis inhibitory protein (NAIP) gene copy distribution and the association of copy number with survival in 232 Chinese spinal muscular atrophy (SMA) patients. The SMN2 and NAIP copy numbers correlated positively with the median onset age (r = 0.72 and 0.377). The risk of death for patients with fewer copies of SMN2 or NAIP was much higher than for those with more copies (P < .01). The survival probabilities at 5 years were 5.1%, 90.7%, and 100% for 2, 3, and 4 SMN2 copies and 27.9%, 66.7%, and 87.2% for 0, 1, and 2 NAIP copies, respectively. Our results indicated that combined SMN1-SMN2-NAIP genotypes with fewer copies were associated with earlier onset age and poorer survival probability. Better survival status for Chinese type I SMA might due to a higher proportion of 3 SMN2 and a lower rate of zero NAIP., (© The Author(s) 2014.)