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Rare copy number variations have been linked to an important source of mutation in many psychopathological traits and neurodevelopmental disorders. In this study, we describe a Taiwanese girl with mental retardation and mild macrocephaly who underwent a childhood psychological evaluation for several years first. When she was 5 years old, she came to our hospital for further diagnosis. We conducted molecular cytogenetic tests and confirmed she actually has Sotos syndrome. We compared our case with two others with very similar deletion regions, but their phenotypes were heterogeneous. Sotos syndrome is very rare in Taiwan, and it is suggested that genetic analysis should be considered early if symptoms of this case are observed.

Autophagy, a double-edged sword for cell survival, is the research object on 2016 Nobel Prize in Physiology or Medicine. Autophagy is a molecular mechanism for maintaining cellular physiology and promoting survival. Defects in autophagy lead to the etiology of many diseases, including diabetes mellitus (DM), cancer, neurodegeneration, infection disease and aging. DM is a metabolic and chronic disorder and has a higher prevalence in the world as well as in Taiwan. The character of diabetes mellitus is hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and failure of producing insulin on pancreatic beta cells. In T2DM, autophagy is not only providing nutrients to maintain cellular energy during fasting, but also removes damaged organelles, lipids and miss-folded proteins. In addition, autophagy plays an important role in pancreatic beta cell dysfunction and insulin resistance. In this review, we summarize the roles of autophagy in T2DM.

Background Obesity is one of the main causes of preventable death. Complications of childhood obesity include cardiovascular risk, impaired glucose tolerance, type 2 diabetes mellitus, and acanthosis nigricans (AN; associated with obesity as a manifestation of cutaneous insulin resistance). An interaction between AN and obesity as well as a detailed mechanism for the pre- and co-obesity appearance of AN in children are still to be revealed. Purposes This research tries to assess involvement of the insulin/insulin-like growth factor (IGF) receptor pathway in childhood pre- and co-obesity AN via a study of the association of polymorphisms of the INSR, IRS1, and IGF1R genes with pre- and co-obesity AN. Methods In total, 99 children with pre- and co-obesity AN and 100 healthy controls were genotyped and analyzed by the polymerase chain reaction-restriction fragment length polymorphism method. Results Intergroup frequency differed starkly for INSR His1085His and IGF1R IVS7-20, but not in the IRS1 Ala804Ala or IGF1R Thr766Thr genotypes. The T allele of INSR His1085His and C allele of IGF1R IVS7-20 both conferred a starkly( p=0.04 and 2.84E-6 = 2.84 x 10 −6 , respectively)higher risk for AN. Conclusion The above findings suggest that certain genetic variants in insulin/insulin-like growth factor (IGF) receptor pathway might be correlated with the appearance of AN prior to or concurrent with obesity, and also reveal the insulin/IGF receptor pathway as crucial in pre- and co-obesity AN.

Background: Recent research suggests that Tourette’s syndrome (TS) may result from a defect in the dopamine system. Several candidate gene polymorphisms have been implicated in attention deficit hyperactivity disorder, including the dopamine transporter (DAT1 )a nd dopamine b-hydroxylase (DBH) genes. A high rate of comorbidity between attention deficit hyperactivity disorder and TS indicates that they may share the same pathophysiology. Purpose: We aimed to test the hypothesis that the dopamine gene might play a role in TS. Methods: An association study, using an independent sample of patients from the midland region of Taiwan, was performed to investigate whether DAT1 and DBH gene polymorphisms can be used as markers of susceptibility to TS. A total of 160 children with TS and 83 normal controlparticipantswereincludedinthestudy.Polymerasechainreactionwasusedtoidentify polymorphisms in the DAT1 (40 bp VNTR) and DBH (TaqI A2) genes. Genotypes and allelic frequencies for the DAT1 and DBH gene polymorphisms in both groups were compared. Results: The results showed that genotypes and allelic frequencies in both groups were not significantly different. The most common genotype for DAT1 (40 bp VNTR) was the 10,10 homozygote in both groups. The most common genotype for DBH (TaqI A2) was the T homozygote in both groups. Conclusion: These data suggest that the DAT1 and DBH genes may not be useful markers to predict susceptibility to TS.

Pitt-Hopkins syndrome (PTHS), caused by a TCF4 gene mutation, is a condition characterized by intellectual disability and developmental delay, breathing anomalies, epilepsy, and distinctive facial dysmorphism [1]. Its diverse clinical appearance causes pediatricians to confuse it with Angelman syndrome, which is considered one of the family members of Angelman-like syndrome. Herein, we report on a 4 y/o boy with PTHS and discuss its similarities and differences with Angelman syndrome. In doing so we hope to provide a feasible pathway to diagnose rare diseases, especially Angelman-like syndrome.

Diabetic retinopathy (DR) is one of the most feared complications of diabetes and is a leading cause of acquired blindness in working adults. The prevalence of undiagnosed diabetes in Taiwan is about 4%, and the annual incidence of T2D (Type 2 Diabetes) in Taiwan is 1.8% following the 1985 WHO criteria. Multiple mechanisms have been shown in T2DR with some signaling pathways, including the polyol pathway, PKC pathway, AGEs pathway, and MAPK pathway. However, the cause of vision loss in diabetic retinopathy is complex and remains incompletely understood. Herein, we try to fully understand the new concepts regarding hyperglycemia-induced biochemical pathways contributing to DR pathophysiology. Our work may be able to provide new strategies for the prevention and treatment of diabetic vascular complications.

We report the case of a 2-year-old male with congenital symmetric facial diplegia, and bilateral paralysis of abduction of the eyes. Findings were compatible with a diagnosis of Mobius syndrome. Routine G-banded chromosome analysis revealed a mosaic karyotype with 40 cells showing normal 46,XX and 10 cells showing normal 46,XY. An XX male attributed to XX/XY mosaicism was diagnosed. The phenotype of our patient did not coincide with any described form of XX reversal syndrome, but and was a unique combination of both syndromes. The disorder of this patient is likely to represent a genetic condition with pleiotropic effects on brain development and sex determination, providing adding further evidence for the heterogeneity of Mobius syndrome and sex reversal syndromes.

In encephalopathic infants, cerebrospinal fluid hyperglycinemia and elevated cerebrospinal fluid to plasma glycine ratio are considered pathognomonic of nonketotic hyperglycinemia (NKH). We present a case of NKH complicated by neonatal intractable seizures. Increased ratio of cerebrospinal fluid to plasma glycine concentrations of 0.28 was seen as a strong diagnostic indicator of nonketotic hyperglycinemia. Evaluating sick neonates with hypotonia, encephalopathy, and/or seizures is a diagnostic challenge. NKH should be considered; elevated cerebrospinal fluid/plasma glycine ratio will allow correct identification and treatment more often in the future.

Background:Multiple hereditary exostoses (MHE) is characterized by multiple benign projections of bone capped by cartilage, most numerous in metaphyses of long bones. HME are usually inherited in autosomal dominant mode, chief genes EXT1 and EXT2. Methods:Two MHE patients were identified from clinic and enrolled in genetic study, complete coding regions of EXT1 and EXT2, including intron/exon boundaries, sequenced via DNA samples drawn from participants. Results:DNA sequencing revealed mutant EXT1 gene in both cases, within which frame-shift mutation c.447delC (p.Ser149fsX156) in exon1 and nonsense mutation c.2034T>G (p.Tyr678X) in exon10, emerged. Neither mutation was detected in control group. Conclusions:Our results extended the spectrum of EXT1 mutations, revealing similar incidence of EXT1 and EXT2 in Taiwanese MHE patients.

Paroxysmal kinesigenic dyskinesia (PKD), a rare paroxysmal movement disorder often misdiagnosed as epilepsy, is characterized by recurrent, brief dyskinesia attacks triggered by sudden voluntary movement. Pathophysiological mechanism of PKD remains not well understood. Ion channelopathy has been suggested, since the disease responds well to ion channel blockers. Mutations in proline-rich transmembrane protein 2 (PRRT2) were recently identified in patients with familial PKD. To extend these genetic reports, we studied a family with clinical manifestations of familial PKD responding well to low dose carbamazepine. Therapeutic dose ranged from 1.5 to 2.0 mg/ kg/day, below that in seizure control. One insertion mutation c.649_650insC (p.P217fsX7) was identified in three patients of the family. This study avers PRRT2’s high sensitivity for PKD phenotype. Identification of genes underlying pathogenesis will enhance diagnosis and treatment. Function of PRRT2 and its role in PKD warrant further investigation.

Interstitial deletions of the long arm of chromosome 3 have, to our knowledge, been reported in only eleven patients; detailed genotype- phenotype correlations are not well established. Here we describe a case with interstitial deletion involving 3q25.33 region. Dysmorphic features and developmental delay lead to clinical genetic and enzyme assessment. Low alpha-hexosaminidase level is also noted, which imply Mucopolysaccharidosis(MPS) IIIB.

* Corresponding author. Department of Pedia E-mail address: a2340961@yahoo.com.tw 2211-8020/$ e see front matter Copyright a doi:10.1016/j.biomed.2012.04.001 A 12-year-old girl, presented to the Outpatient Department with congenital nonprogressive cranial-facial-digital abnormalities and normal developmental milestones, had a past medical history of congenital heart disease (atrial septal defect, tricuspid valve regurgitation) under long-term followup. Clinically, specific phenotype was characterized by widely separated eyes (hypertelorism), broad nasal root, bifid nasal tip, clinodactyly over left 5th finger and slim fingers Fig. 1 (Panel A,B and C). Computed tomography of her head revealed no skull asymmetry or brachycephaly (Panel D). Her mother showed similar characteristics but with facial asymmetry (Panel E) due to isolated right coronal suture craniosynostosis that had received surgical correction. Although craniofrontonasal dysplasia was our first impression of diagnosis according to the index case’s clinical manifestations, mode of inheritance (most likely autosomal dominant or X-linked dominant disorder) and a hint of isolated craniosynostosis from her mother, several disorders having similar symptoms to those of craniofrontonasal dysplasia, including Aarskog syndrome (widely spaced eyes and broad nose; but lack of low-set ear, short, broad hands with stubby hands, genital malformations and mental retardation), Frontonasal