Novel compound heterozygous mutations in the PEX1 gene in two Chinese newborns with Zellweger syndrome based on whole exome sequencing

Meng-Meng Ge; LiYuan Hu; ZhiHua Li; GuoQiang Cheng; Kai Yan; YanTing Kong; HuiJun Wang; Lin Yang; WenHao Zhou

doi:10.1016/j.cca.2017.04.016

Novel compound heterozygous mutations in the PEX1 gene in two Chinese newborns with Zellweger syndrome based on whole exome sequencing

Clin Chim Acta. 2017 Jul:470:24-28. doi: 10.1016/j.cca.2017.04.016. Epub 2017 Apr 19.

Authors

Meng-Meng Ge¹, LiYuan Hu¹, ZhiHua Li¹, GuoQiang Cheng¹, Kai Yan¹, YanTing Kong¹, HuiJun Wang², Lin Yang³, WenHao Zhou⁴

Affiliations

¹ Department of Neonates, Children's Hospital of Fudan University, Shanghai, China.
² Birth Defect Laboratory, Children's Hospital of Fudan University, Shanghai, China.
³ Clinical Genetic Center, Children's Hospital of Fudan University, Shanghai, China.
⁴ Department of Neonates, Children's Hospital of Fudan University, Shanghai, China; Birth Defect Laboratory, Children's Hospital of Fudan University, Shanghai, China. Electronic address: zhouwenhao@fudan.edu.cn.

PMID: 28432012
DOI: 10.1016/j.cca.2017.04.016

Abstract

Peroxisome biogenesis disorders (PBDs) represent a spectrum of human genetic disorders that are characterized by damaged peroxisome assembly. In the newborn period, the characteristics of affected patients include dysmorphic facial features, neonatal hypotonia, seizures, ocular abnormalities, poor feeding, liver cysts with hepatic dysfunction and skeletal defects. These can be caused by a defect in at least 14 different PEX genes. In this study, whole-exome sequencing (WES) was performed on samples from two Chinese newborns with clinical features of Zellweger syndrome. WES identified two novel mutations (c.2416+1G>T and c.2489delT) in patient 1 and another two novel mutations (c.1483+1G>A and c.1727dupG) in patient 2 in the PEX1 gene. All four mutations have a serious influence on the protein function, which also highlights the power of WES, particularly in clinically challenging cases.

Keywords: Newborn; PEX1; Whole-exome sequencing; Zellweger syndrome.

Publication types

Case Reports

MeSH terms

ATPases Associated with Diverse Cellular Activities / genetics*
Asian People / genetics*
Base Sequence
Exome Sequencing*
Heterozygote*
Humans
Infant, Newborn
Male
Membrane Proteins / genetics*
Mutation*
Peroxisomes / genetics
Phenotype
Zellweger Syndrome / genetics*
Zellweger Syndrome / pathology

Substances

Membrane Proteins
ATPases Associated with Diverse Cellular Activities
PEX1 protein, human