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Journal of Pediatric Neurology 2020; 18(01): 033-038
DOI: 10.1055/s-0038-1677489
Case Report
Georg Thieme Verlag KG Stuttgart · New York

A De novo Loss-of-Function Mutation in PAFAH1B1 Identified in a Single Case with Agyria–Pachygyria Complex

Yali Ou
1   Department of Cardiology, First Xiangya Hospital, Central South University, Changsha, Hunan, China
2   Experimental Medicine Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States
,
Bingwu Xiang
3   Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Zhejiang, China
,
Liu Yang
3   Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Zhejiang, China
,
Wei Chen
4   Department of Radiology, The Second Affiliated Hospital of Wenzhou Medical University, Zhejiang, China
,
Xiang Chen
3   Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Zhejiang, China
,
Tao Cai
2   Experimental Medicine Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States
› Author Affiliations Funding This study was supported by the research funding from the Chinese Ministry of Health Project (No: 201302002 to XC). This research was supported in part by the intramural research program of the NIH, NIDCR.
Further Information

Publication History

12 November 2018

06 December 2018

Publication Date:
07 January 2019 (online)

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Abstract

To identify genetic causes in affected infants with abnormalities of brain development, including malformations of cortical development–associated neuropsychological disorders, affected infants were recruited based on their clinical examination and cranial imaging studies. Trio whole-exome sequencing (WES), bioinformatic analysis, and genotype–phenotype correlations were performed for 20 affected subjects to identify candidate mutations, followed by Sanger sequencing for further verification. In the present study, we identified a de novo heterozygous mutation (c.265C > T, p.R89*) of the PAFAH1B1 gene in the affected child with epilepsy, speech impairment, and cerebral palsy. The mutation was predicted to be a null loss-of-function allele, which was not found in ExAC and the Chinse Han Exome Sequences databases. Magnetic resonance imaging of the brain demonstrated bilateral parieto-occipital and temporal lissencephaly as well as frontal partial pachygyria in the affected child. This is the first case with agyria–pachygyria complex due to a nonsense mutation in the Chinese population identified by a trio WES approach.

Keywords

lissencephaly - PAFAH1B1 - trio whole-exome sequencing - brain development
 

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