Analysis of SATB2 gene mutation in a child with Glass syndrome / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical characteristics and genetic basis of a child affected with Glass syndrome.@*METHODS@#Clinical manifestations and auxiliary examination results of the child were analyzed. Potential mutation was detected with next generation sequencing and validated by Sanger sequencing.@*RESULTS@#The child has featured growth and mental retardation, delayed speech, cleft palate, crowding of teeth, and downslanting palpebral fissures. DNA sequencing revealed a de novo heterozygous missense mutation c.1166G>A (p.R389H) in exon 8 of the SATB2 gene in the child.@*CONCLUSION@#The heterozygous mutation c.1166G>A (p.R389H) of the SATB2 gene probably account for the Glass syndrome in the patient.

Identification of a novel SYNGAP1 mutation in a child with intellectual disability / 中华医学遗传学杂志

OBJECTIVE@#To report on a child with mental retardation caused by SYNGAP1 gene mutation.@*METHODS@#Peripheral blood samples were collected from the proband and her parents. High throughput sequencing (HTS) was employed for screening for potential mutation in the patient. Suspected mutation was validated by Sanger sequencing of the child and her parents.@*RESULTS@#By HTS, a previously unknown mutation [c.1656C>A (p.C552*)] was found in exon 10 of the SYNGAP1 gene in the proband. Sanger sequencing confirmed the heterozygous nature of the mutation and that neither of her parents carried the same mutation.@*CONCLUSION@#The dysmorphism and developmental delay of the child were probably due to the pathogenic mutation of the SYNGAP1 gene. HTS can facilitate elucidation of the genetic etiology with efficiency, which has great significance in the diagnosis, treatment and prognosis of the child.

Congenital disorder of glycosylation type Ⅰg: a case report and literature review / 中国新生儿科杂志

Objective To study the clinical features,diagnosis,genetic characteristics and treatment of congenital disorder of glycosylation type Ⅰg (CDG-Ⅰg) and to raise the awareness of CDG-Ⅰg among the clinicians.Method The data of one child with CDG-Ⅰg admitted to Shanghai Children's Medical Center affiliated to Shanghai Jiaotong University School of Medicine was studied retrospectively.Literatures were retrieved with key words including "congenital glycosylation disorder Ⅰg","ALG12","congenital glycosylation defect Ⅰg","CDG-Ⅰg" and "congenital disorder" in the Chinese knowledge network,VP database,Wanfang database,Biomedicine,PubMed and the Web of Science database from data established until January 2018.We summarized the clinical and genetic characteristics of CDG-Ⅰg.Result An one-day-old male infant admitted to the Hospital due to "poor response with hypoglycemia" manifested with facial deformity,hypotonia,inverted nipples,micropenis and undescended testes.He had intermittent hypoglycemia and recurrent infection,treated with antimicrobials,glucose rehydration and hormone therapy.Serum insulin,growth hormone level,blood and urine metabolic screening were normal.The patient was compound heterozygous for ALG12 mutations,c.432C ＞ A,p.Cys144 * and c.904T ＞ C,p.Tyr302His,each of his parents carried a pathogenic mutation.The patient died in follow-up for unknown reasons.No reported cases of CDG-Ⅰg from China have so far been reported yet.We reviewed the other 8 cases CDG-Ⅰg (4 males and 4 females) born in foreign countries,5 of them with neonatal onset.Common clinical manifestaions include facial deformity,hypotonia,hypogenitalism,coagulopathy,hypoimmunity,recurrent infection,electroyte imbalance etc.The ALG12 gene has 11 mutation sites.Conclusion CDG-Ⅰg is a rare autosomal recessive disorder.Most reported patients had onset in neonatal period.It seems that the association of facial deformity,psychomotor retardation,hypotonia,coagulopathy,male hypogenitalism and hypoglycemia might be a clue to the diagnosis of CDG-Ⅰg.Gene detection of ALG12 can confirm the diagnosis.This disorder has no specific treatment yet.

Clinical-grade gene curation strategy in the development of short stature related gene panel by next generation sequencing / 中华检验医学杂志

Objective Design short stature panel with gene curration strategy.Methods The gene curation process was introduced in detail.The strength of a gene-disease relationship was evaluated based on publicly available genetic and experimental evidence.This process in short stature panel design and its effect on gene selection was further demonstrated.Results After gene curation, the number of gene in list was effectively decreased from 1 276 to 705.The panel sequencing reached a diagnosis rate of 19.7% among a cohort of 371 nation-wide ascertained short stature patients.The gene curation process reduced the risk of false positive findings and decreased diagnostic cost and working hours without affecting the diagnosis rate.Conclusion Gene curation is an important step for NGS-based test and should be widely exercised.