Search

Mandibular hypoplasia, deafness, progeroid feature, and lipodystrophy syndrome (MDPL, MIM# 615381) is an extremely rare and recently recognized early adult onset of progeroid syndrome, with features of generalized lipodystrophy, dysmorphic features, telangiectasia, early onset hearing loss, insulin resistance, and dyslipidemia. Here, we present a 31‐year‐old Chinese woman with MDPL, harboring the recurrent pathogenic variant p.(Ser605del) in POLD1, illustrating the evolving manifestations of this premature aging disorder from infancy to adulthood. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of mitochondrial diseases (MD) in Hong Kong (HK) and to evaluate the clinical characteristics and genetic landscape of MD patients in the region., Methods: This study retrospectively reviewed the phenotypic and molecular characteristics of MD patients from participating public hospitals in HK between January 1985 to October 2020. Molecularly and/or enzymatically confirmed MD cases of any age were recruited via the Clinical Analysis and Reporting System (CDARS) using relevant keywords and/or International Classification of Disease (ICD) codes under the HK Hospital Authority or through the personal recollection of treating clinicians among the investigators., Results: A total of 119 MD patients were recruited and analyzed in the study. The point prevalence of MD in HK was 1.02 in 100,000 people (95% confidence interval 0.81-1.28 in 100,000). 110 patients had molecularly proven MD and the other nine were diagnosed by OXPHOS enzymology analysis or mitochondrial DNA depletion analysis with unknown molecular basis. Pathogenic variants in the mitochondrial genome (72 patients) were more prevalent than those in the nuclear genome (38 patients) in our cohort. The most commonly involved organ system at disease onset was the neurological system, in which developmental delay, seizures or epilepsy, and stroke-like episodes were the most frequently reported presentations. The mortality rate in our cohort was 37%., Conclusion: This study is a territory-wide overview of the clinical and genetic characteristics of MD patients in a Chinese population, providing the first available prevalence rate of MD in Hong Kong. The findings of this study aim to facilitate future in-depth evaluation of MD and lay the foundation to establish a local MD registry., (© 2023. The Author(s).)

This study supports training in genetic counseling for obstetricians and adoption of a multidisciplinary approach in the counseling process following prenatal diagnosis of sex chromosome aneuploidy.

Aim: According to the published work, pregnancy termination rates due to prenatal diagnosis of fetal sex chromosome aneuploidies (SCA) vary widely. Some potentially modifiable and non-modifiable factors have been reported to be associated with parental decision. This study aimed to evaluate the rate of pregnancy termination for fetal SCA and the factors influencing parents' decisions in Hong Kong., Methods: This was a 21-year retrospective cohort study of parents' decisions following prenatal diagnosis of SCA. Univariate and multivariate analyses for the association between demographic factors, prenatal factors, or counseling provided and decision-making were conducted., Results: The study included 399 pregnancies with prenatal diagnosis of SCA and the overall termination rate was 55.6% (91.7%, 48.0%, 23.4%, 4.8%, and 22.7% for 45,X, 47,XXY, 47,XXX, 47,XYY, and mosaicism, respectively). Pregnancies with ultrasound abnormalities were associated with higher termination rates than pregnancies with normal ultrasound findings (91.3% vs 28.3%, P < 0.0001). From multivariate regression analysis on 226 pregnancies with normal ultrasound examination, a higher likelihood to terminate was found in pregnancies affected by 45,X and 47,XXY (adjusted odds ratio, 4.72, P < 0.0001). Increased maternal age and history of infertility were associated with lower likelihood to terminate (adjusted odds ratio, 0.9, P = 0.012; and 5.12, P = 0.038, respectively). The pregnancy termination rate declined over time., Conclusion: A significant correlation was found between the termination of SCA-affected pregnancy and the presence of fetal sonographic abnormalities, type of SCA, maternal age, and presence of infertility., (© 2017 Japan Society of Obstetrics and Gynecology.)

Background: Sizing of FMR1 trinucleotide repeats in the clinical laboratory requires the use of capillary sequencer by PCR, or by a labor intensive measurement using Southern blot method. Our aim was to validate an accurate and robust PCR assay for quantification of CGG repeats., Methods: We performed an analytical and clinical validation of a new PCR-based method that utilizes a low-cost capillary electrophoresis instrument and the FragilEase™ reagent kit. First, analytical performance was demonstrated on 12 Coriell reference samples comprising normal through full mutations. Subsequently, a cohort of 112 archived clinical DNA samples, enriched for premutation and full mutations, was analyzed., Results: All samples were amplified successfully. Quantification of repeat numbers was interpreted by the use of standards with known repeats. Twenty-five full-mutation samples were successfully amplified with the largest allele size measured at 1380 repeats. The repeat numbers from the new assay were concordant with those obtained with the reference method. The intra-assay (CV<2.5%) and inter-assay imprecision was within 1 CGG repeat., Conclusion: This new PCR-based method is reproducible and capable of identifying all Fragile X alleles. It is an accurate and robust method that facilitates Fragile X testing in a broader spectrum of clinical laboratories., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Von Hippel-Lindau (VHL) syndrome is an autosomal dominant familial cancer syndrome predisposing the affected individuals to multiple tumours in various organs. The genetic basis of VHL in Southern Chinese is largely unknown. In this study, we characterized the mutation spectrum of VHL in nine unrelated Southern Chinese families., Methods: Nine probands with clinical features of VHL, two symptomatic and eight asymptomatic family members were included in this study. Prenatal diagnosis was performed twice for one proband. Two probands had only isolated bilateral phaeochromocytoma. The VHL gene was screened for mutations by polymerase chain reaction, direct sequencing and multiplex ligation-dependent probe amplification (MLPA)., Results: The nine probands and the two symptomatic family members carried heterozygous germline mutations. Eight different VHL mutations were identified in the nine probands. One splicing mutation, NM&#95;000551.2: c.463+1G > T, was novel. The other seven VHL mutations, c.233A > G [p.Asn78Ser], c.239G > T [p.Ser80Ile], c.319C > G [p.Arg107Gly], c.481C > T [p.Arg161X], c.482G > A [p.Arg161Gln], c.499C > T [p.Arg167Trp] and an exon 2 deletion, had been previously reported. Three asymptomatic family members were positive for the mutation and the other five tested negative. In prenatal diagnosis, the fetuses were positive for the mutation., Conclusions: Genetic analysis could accurately confirm VHL syndrome in patients with isolated tumours such as sporadic phaeochromocytoma or epididymal papillary cystadenoma. Mutation detection in asymptomatic family members allows regular tumour surveillance and early intervention to improve their prognosis. DNA-based diagnosis can have an important impact on clinical management for VHL families.

We present an evaluation of the diagnosis, management and outcome of a pair of heterokaryotypic monozygotic dichorionic twins. The heterokaryotype was an incidental finding from an amniocentesis performed for prenatal diagnosis of beta-thalassaemia major in a pair of dichorionic twins. Monozygocity was revealed by QF-PCR showing identical short tandem repeat markers on chromosomes 21, 18, 13, X and Y. The twins were heterokaryotypic for duplication chromosome 2q13-q23.3, as shown by array comparative genomic hybridization. Selective foeticide was performed. This case demonstrates that heterokaryotypic monozygotic dichorionic twins are a genetic possibility that does occur., (2009 S. Karger AG, Basel)

We report on a newborn baby with partial trisomy 13 who presented with multiple dysmorphic features and hyperinsulinaemic hypoglycaemia. Cytogenetic study on peripheral blood lymphocytes showed 47,XY,+mar in all cells analysed; fluorescent in situ hybridisation showed that the marker was solely derived from chromosome 13. The final karyotype was 47,XY,+del(13)(q14q32). Milk formula through a nasogastric drip and intravenous glucose infusion were given to prevent further hypoglycaemia. However, the baby developed occasional episodes of hypoglycaemia during bolus feeding. Hence, diazoxide was given, at a dosage of 10 mg/kg per day from day 24. Thereafter, no hypoglycaemic episodes were detected. Subsequent follow-up revealed satisfactory growth, global developmental delay, and left divergent squint.

Interstitial deletions of the long arm of chromosome 3 are uncommon. Most cases are related to the blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), which is mapped to 3q23. We report on a case with a de novo chromosomal deletion of 3q23 and 3q25. We review the literature on the reported cases of 3q deletion and find that the condition of our patient is not typical of the BPES. Rather, she shares similarity to a patient with Wisconsin syndrome, first discovered in 1976., (Copyright 2003 Wiley-Liss, Inc.)

Basal cell nevus syndrome (BCNS) is an autosomal dominant disease characterized by the presence of multiple basal cell carcinomas, odontogenic keratocysts, palmoplantar pits, and calcification in the falx cerebri caused by mutational inactivation of the PTCH gene. To investigate the molecular basis of BCNS in Chinese, we did a mutational analysis of the PTCH gene by performing denaturing high-performance liquid chromatography in three BCNS families. In this study, three novel mutations, two 1-bp frameshift insertions, i.e., 1468insA and 2392insC, and one 8-bp deletion, i.e., IVS5 + 1delGTAAGTGT, affecting a donor splice site, were identified. All the mutations cause a shift of the open reading frames and lead to premature termination of PTCH protein translation. Our results showed that mutational inactivation of the PTCH gene causes BCNS in Chinese.

The records of 40 nongrowing open bite patients treated with orthodontics and maxillary surgery were divided into two groups and evaluated. The extrusion group (n = 19) included those patients who had presurgical maxillary incisor extrusion of at least 1.5 mm. In the nonextrusion group (n = 21), the maxillary incisors were maintained or intruded prior to surgery. Statistical analysis showed no relationship between presurgical extrusion of the maxillary incisors and the stability of open bite correction; the maxillary incisors were generally stable long term in both groups. Overbite decreased a mean of -0.97 mm in the extrusion group and -0.67 mm in the nonextrusion group during the mean 5-year 10-month follow-up period after appliance removal. Twenty-five percent (10 of 40, 5 from each group) of the sample had no incisal overlap long term. These findings suggest that a moderate amount of presurgical incisor extrusion or lack of extrusion are stable long term and have little influence on posttreatment stability of open bites. The decrease in overbite observed after treatment may result from the influence of various dental, skeletal, and soft tissue factors rather than from any single factor.

Objective: To study the role of chromosomal aberration in the causation of recurrent spontaneous abortion (RSA) in Chinese population., Methods: A total of 514 Chinese couples with 2 or more spontaneous abortions at less than 24 weeks of gestation were included. For each proband, a minimum of 13 metaphases were analyzed by G-banding. Additional cells (usually 50-100 cells) were screened when mosaicism was suspected. Chi 2 test was used to compare the number and frequency of couples with and without balanced translocation with respect to whether liveborn was present or absent. Chi 2 test for trend was used to show whether a correlation existed between the occurrence of balanced translocation and the number of spontaneous abortions at ascertainment., Results: The overall incidence of chromosome anomaly was 51 out of 514 (9.92%). Chi 2 test for trend analysis showed that the chance of one member of a couple being a balanced carrier increased with the number of spontaneous abortions. The chance of finding translocation in couples with liveborn was higher than that in couples without liveborn, but the difference was not statistically significant. We also found that pericentric inversion 9 did not play an important role in the causation of recurrent abortion., Conclusions: Cytogenetic analysis is indicated in couples with 2 or more spontaneous abortions and the chance of finding chromosomal aberration increases with the number of abortions at the time of ascertainment.