Clinical and Mutational Features of Three Chinese Children with Congenital Generalized Lipodystrophy

Abstract

Objective:To investigate the clinical and molecular features of congenital generalized lipodystrophy (CGL) in three Chinese patients with various typical manifestations.Methods:Data on clinical symptoms, results of laboratory analyses, and previous treatments in three Chinese patients were collected by a retrospective review of medical records. All coding regions and adjacent exon–intron junction regions of AGPAT2 and BSCL2 genes were amplified by polymerase chain reaction and sequenced.Results:Generalized lipodystrophy, acanthosis nigricans, muscular hypertrophy, severe hypertriglyceridemia, and hepatomegaly were features in all three patients. Patient 1 developed diabetes mellitus at the early age of 2 months and he was the youngest CGL patient reported with overt diabetes. Patient 2 was found to have cardiomyopathy when she was aged 6 months. All of the patients were found to have mutations in the BSCL2 gene, but none of these was a novel mutation. We did not find any AGPAT2 mutation in our patients.Conclusion:All of our patients exhibited characteristic features of CGL due to mutations in the BSCL2 gene.

Novel compound heterozygous variant of BSCL2 identified by whole exome sequencing and multiplex ligation‑dependent probe amplification in an infant with congenital generalized lipodystrophy

“…The variant of c.545_546insCCG resulted in a disruptive inframe indel at position 182 (p.Glu182delinsasparg), which may cause the misfolding of the secondary structure of the seipin protein due to the insertion of the basic amino acid arginine and could destabilize the protein structural domain. Given that this variant has only been reported in chinese patients with cGl (13,14), it is a recurrent pathogenic variant in the chinese population.…”

“…The maternally inherited variant c.545_546insccG is rare in the general population (PM2) (13,14). it has been reported in trans with a pathogenic variant at least twice (PM3_Strong) and shortens the protein product (PM4) (13).…”

The neonatal onset diabetes mellitus of Chinese neonate with congenital generalized lipodystrophy 2: a case report

“…Similarly, another report found a child who was diagnosed at 9 months of age with CGL and also developed diabetes 13 years later [ 10 ]. Finally, a series of case reports published by Indumathi et al and Friguls et al, found that children with CGL2 developed diabetes at the age of 4–5 months [ 11 , 13 , 14 ]. In our case study, our neonate developed diabetes at a very early age of 12 days and is the youngest reported CGL patient with diabetes so far.…”

Role of Seipin in Human Diseases and Experimental Animal Models

“…CGL2 patients often have many physical changes, mainly including acanthosis nigricans, hirsutism, muscular hypertrophy, and acromegaly [ 65 , 90 , 93 ]. Additionally, triangular facies [ 65 , 89 , 90 ], large ears [ 74 , 89 , 94 ], prognathism [ 60 ], and hernia [ 14 , 89 , 90 ] have all been reported.…”

“…Apart from the typical features of metabolic disturbances, CGL2 patients also have a greatly increased probability of developing mild to moderate mental disability [ 58 , 60 , 61 , 79 , 95 ]. Occasionally, symptoms of motor neuron impairment such as waddling gait [ 60 ], spastic gait [ 95 ], and developmental language disorders [ 93 ] have been reported.…”