Dataset Information

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

ABSTRACT: Congenital generalized lipodystrophy (CGL) is a clinically and genetically heterogeneous condition with autosomal recessive inheritance. CGL is classified into four subtypes on the basis of causative genes. This study reported on a 2?month?old male infant diagnosed with CGL with generalized lipoatrophy and skin hyperpigmentation. Whole exome sequencing (WES) identified a heterozygous small insertion (c.545_546insCCG) in Berardinelli?Seip congenital lipodystrophy 2 (BSCL2) that was inherited from the infant's mother. Copy number variation analysis using exome data suggested a heterozygous deletion involving exon 3 that was inherited from the infant's father. This finding was confirmed by multiplex ligation?dependent probe amplification test. Gap?PCR revealed breakpoints and confirmed a 1274 bp heterozygous deletion encompassing exon 3 of BSCL2 (c.213?1081_c.294+111). This deletion is different from the founder 3.3 kb deletion involving exon 3 of BSCL2 in the Peruvian population. An 11?bp microhomology at the breakpoints may mediate the deletion, and its presence indicates the independent origins of the exon 3 deletion between Chinese and Peruvian populations. The present results expanded the mutational spectrum of the BSCL2 gene in the Chinese population and suggested that introns 2 and 3 of BSCL2 are prone to recombination. Thus, exon 3 deletion should be considered for patients with CGL2 when only one BSCL2 variant is detected through WES.

SUBMITTER: Xie B

PROVIDER: S-EPMC7185175 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Xie Bobo B Fan Xin X Lei Yaqin Y Yi Shang S Yang Qi Q Wang Jin J Qin Zailong Z Shen Fei F Luo Jingsi J Shen Yiping Y

Molecular medicine reports 20200323 6

Congenital generalized lipodystrophy (CGL) is a clinically and genetically heterogeneous condition with autosomal recessive inheritance. CGL is classified into four subtypes on the basis of causative genes. This study reported on a 2‑month‑old male infant diagnosed with CGL with generalized lipoatrophy and skin hyperpigmentation. Whole exome sequencing (WES) identified a heterozygous small insertion (c.545_546insCCG) in Berardinelli‑Seip congenital lipodystrophy 2 (BSCL2) that was inherited from ...[more]

PMID: 32236581

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Project description:Background:Lamin A/C (LMNA) gene mutations cause a heterogeneous group of progeroid disorders, including Hutchinson-Gilford progeria syndrome, mandibuloacral dysplasia, and atypical progeroid syndrome (APS). Five of the 31 previously reported patients with APS harbored a recurrent de novo heterozygous LMNA p.T10I mutation. All five had generalized lipodystrophy, as well as similar metabolic and clinical features, suggesting a distinct progeroid syndrome. Methods:We report nine new patients and follow-up of two previously reported patients with the heterozygous LMNA p.T10I mutation and compare their clinical and metabolic features with other patients with APS. Results:Compared with other patients with APS, those with the heterozygous LMNA p.T10I mutation were younger in age but had increased prevalence of generalized lipodystrophy, diabetes mellitus, acanthosis nigricans, hypertriglyceridemia, and hepatomegaly, together with higher fasting serum insulin and triglyceride levels and lower serum leptin and high-density lipoprotein cholesterol levels. Prominent clinical features included mottled skin pigmentation, joint contractures, and cardiomyopathy resulting in cardiac transplants in three patients at ages 13, 33, and 47 years. Seven patients received metreleptin therapy for 0.5 to 16 years with all, except one noncompliant patient, showing marked improvement in metabolic complications. Conclusions:Patients with the heterozygous LMNA p.T10I mutation have distinct clinical features and significantly worse metabolic complications compared with other patients with APS as well as patients with Hutchinson-Gilford progeria syndrome. We propose that they be recognized as having generalized lipodystrophy-associated progeroid syndrome. Patients with generalized lipodystrophy-associated progeroid syndrome should undergo careful multisystem assessment at onset and yearly metabolic and cardiac evaluation, as hyperglycemia, hypertriglyceridemia, hepatic steatosis, and cardiomyopathy are the major contributors to morbidity and mortality.

Dataset Information

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

Publications

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

Similar Datasets

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