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; Fan,Xin; Lei,Yaqin; Yi,Shang; Yang,Qi; Wang,Jin; Qin,Zailong; Shen,Fei; Luo,Jingsi; Shen,Yiping

doi:10.3892/mmr.2020.11036

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

Authors:
- Bobo Xie
- Xin Fan
- Yaqin Lei
- Shang Yi
- Qi Yang
- Jin Wang
- Zailong Qin
- Fei Shen
- Jingsi Luo
- Yiping Shen
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Affiliations: Department of Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi 530023, P.R. China
Published online on: March 23, 2020 https://doi.org/10.3892/mmr.2020.11036
Pages: 2296-2302
Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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