Clinical and molecular characterization of two Chinese patients with Type 2 congenital generalized lipodystrophy

摘要

Abstract Background Type 2 congenital generalized lipodystrophy (CGL2, OMIM 269700 ) is a rare autosomal recessive disease, characterized by the generalized absence of adipose tissue at birth or in early infancy. Pathogenic variants in BSCL2 gene have been reported to be responsible for CGL2. The aim of this study is to analyze the clinical and genetic characteristics of two Chinese patients with CGL2, and with particular focus on the BSCL2 gene sequence variants. Methods Medical history, clinical manifestations, physical examination, laboratory data, and ultrasonography findings were analyzed for the two patients with CGL2. Blood samples from both families were obtained for genetic testing. Next generation sequencing for the 2742-gene inherited disease panel were conducted. Results Two patients had similar physical appearances including a conspicuous generalized lack of body fat since birth, extreme muscularity, face with empty cheeks, hirsutism and skin hyperpigmentation especially around necks and armpits; both had intellectual disability, alone with psycho-behavioral issues including tantrum and aggression. One patient exhibited multiple signs of overgrowth such as advanced bone age and macropenis. Laboratory data revealed hypertriglyceridemia, hypercholesterolemia, and low high-density lipoprotein cholesterol concentration. Ultrasound showed hepatomegaly in both patients and renal hypertrophy in patient 2. Echocardiography exams were normal. Both were treated with low-fat, high-carbohydrate diet. Molecular testing confirmed the clinical diagnosis of CGL, specifically CGL2 by detecting a homozygous variant (c.782dupG/p.Ile262Hisfs*12) in BSCL2 gene in patient 1, and compound heterozygous mutations (c. 713G>A/p.Gly238Asp and c.782dupG/p.Ile262Hisfs*12) in patient 2. Conclusion We describe two patients with classic clinical manifestations of CGL2 confirmed by genetic sequence analysis. A novel variant in BSCL2 gene was detected in one patient (c.713G>A/p.Gly238Asp). Highlights ? Two unrelated Chinese patients with CGL2 diagnosed by genetic sequencing. ? A compound heterozygous mutation was found in patient 2 with CGL2. ? Patient 2 had renal hypertrophy, an uncommon feature of CGL2. ? The c.713G>A/p.Gly238Asp is a novel variant of the BSCL2 gene.