Clinical features and gene analysis in a family with type 2 congenital generalized lipodystrophy due to BSCL2 mutation / 中华内分泌代谢杂志

Objective:To investigate the clinical and genetic features in a family with type 2 congenital generalized lipodystrophy, and to improve the understanging of this disease.Methods:The clinical symptoms, results of the laboratory, and radiography examinations of the patient and his family members were analyzed. The whole exome sequencing and Sanger validation were used to determine the genetic cause of the disease.Results:Generalized lipodystrophy, impaired liver function, severe hypertriglyceridemia, and acanthosis nigricans were found in the proband. His serum leptin level was much lower than normal value. The proband and three members of this family were confirmed to have insertion mutation at exon 5 of BSCL2 gene. The site was mutated from TTC to TCGGTC, resulting in the replacement of glutamate by aspartate and arginine. The mutation in proband was homozygote, and his father, mother, and brother were heterozygous.Conclusions:The mutation in exon 5 c. 545_546insCCG of BSCL2 gene leads to the occurrence of type 2 congenital generalized lipodystrophy.

Congenital generalized lipodystrophy caused by mutation of BSCL2 gene: a case report and literature review / 临床儿科杂志

Objective To explore the clinical and genetic characteristics of congenital generalized lipodystrophy (CGL). Method The clinical data of one child with CGL caused by BSCL2 gene mutation were analyzed retrospectively and relative literature were reviewed. Results A 2-year-9-month old girl had clinical manifestations of a lack of subcutaneous fat, acanthosis nigricans, hepatolienomegaly and mild hypophrenia. Laboratory examinations showed hypertriglyceridemia, hyperinsulinemia and cardiomyopathy. The peripheral blood from the child and her parents were collected and 4 genes, AGPAT2, BSCL2, CAV1 and PTRF, were sequenced by Sanger. The results showed a heterozygous mutation of BSCL2 gene from maternal frameshift (c.567-568delGA, p.E189EfsX12) and paternal nonsense mutation (c.565G>T,p.E189X) respectively in the child, and both mutations were pathogenic ones. By a literature review, it is known that BSCL2 gene mutation is the most common cause of in Asian. In CGL with BSCL2 gene mutation, the commom clinical manifestations include disappearance of systemic adipose tissue, acathosis nigricans and hepatomegaly, and the incidence of myocardial infarction and mental retardation were 40% and 30% respectively. Conclusion The main clinical manifestations of CGL caused by BSCL2 gene mutation were loss of systemic adipose tissue and metabolic disorder at an early age. It was often accompanied by myocardial lesions and mental retardation. Gene diagnosis analysis should be made as earliest possible time for the children suspected of this disease.

Distal Hereditary Motor Neuropathy Type V (dHMN-V) With N88S Mutation in BSCL2 Gene

Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene is known to be associated with different clinical phenotypes; Silver syndrome, Charcot-Marie-Tooth type 2 with a dominant hand involvement and distal hereditary motor neuropathy type V (dHMN-V). Up to now, only two heterozygous mutations (N88S and S90L) in BSCL2 have been reported. We identified a N88S BSCL2 mutation in a dHMN-V family with a spastic gait by whole-exome sequencing. To our knowledge, this is the first report of a N88S BSCL2 mutation in Korean patient.