A Novel Mutation in FRMD7 Causing X-linked Idiopathic Congenital Nystagmus in a Large Family

Overview

Journal Mol Vis

Specialties Cell Biology
Molecular Biology
Ophthalmology

Date 2008 Feb 5

PMID 18246032

Citations 18

Authors

Xiang He

Feng Gu

Yujing Wang

Jinting Yan

Meng Zhang

Shangzhi Huang

Xu Ma

Affiliations

Soon will be listed here.

Abstract

Purpose: To identify the gene responsible for causing an X-linked idiopathic congenital nystagmus (XLICN) in a six-generation Chinese family.

Methods: Forty-nine members of an XLICN family were recruited and examined after obtaining informed consent. Affected male individuals were genotyped with microsatellite markers around the FRMD7 locus. Mutations were comprehensively screened by direct sequencing using gene specific primers. An X-inactivation pattern was investigated by X chromosome methylation analysis.

Results: The patients showed phenotypes consistent with XLICN. Genotype analysis showed that male affected individuals in the family shared a common haplotype with the selected markers. Sequencing FRMD7 revealed a G>T transversion (c.812G>T) in exon 9, which caused a conservative substitution of Cys to Phe at codon 271 (p.C271F). This mutation co-segregated with all affected individuals and was present in the obligate, non-penetrant female carriers. However, the mutation was not observed in unaffected familial males or 400 control males. Females with the mutant gene could be affected or carrier and they shared the same inactivated X chromosome harboring the mutation in blood cells, which showed there is no clear causal link between X-inactivation pattern and phenotype.

Conclusions: We identified a novel mutation in FRMD7 and confirmed the role of this mutation in the pathogenesis of X-linked congenital nystagmus.

Citing Articles

X-linked FRMD7 gene mutation in idiopathic congenital nystagmus and its role in eye movement: A case report and literature review.

Liu F, Wang M, Liao M, Liu L, Jiang X Front Ophthalmol (Lausanne). 2024; 2:1080869.

PMID: 38983508 PMC: 11182149. DOI: 10.3389/fopht.2022.1080869.

Gene Alterations in a Pakistani Family Associated with Congenital Idiopathic Nystagmus.

Arshad M, Shabbir M, Asif S, Shahzad M, Leydier L, Rai S Genes (Basel). 2023; 14(2).

PMID: 36833273 PMC: 9957179. DOI: 10.3390/genes14020346.

Clinical utility gene card for FRMD7-related infantile nystagmus.

Dawar B, Kuht H, Han J, Maconachie G, Thomas M Eur J Hum Genet. 2021; 29(10):1584-1588.

PMID: 33633368 PMC: 8484540. DOI: 10.1038/s41431-021-00826-9.

A Disease-Causing FRMD7 Variant in a Chinese Family with Infantile Nystagmus.

Wu S, Deng S, Song Z, Xu H, Yang Z, Liu X J Mol Neurosci. 2019; 67(3):418-423.

PMID: 30618027 DOI: 10.1007/s12031-018-1245-5.

Stable cell lines of human SH-SY5Y uniformly expressing wild-type or mutant-type FERM domain containing 7 gene.

Pu J, Mao Y, Xu L, Zheng T, Zhang B Exp Ther Med. 2017; 14(3):2277-2283.

PMID: 28962155 PMC: 5609196. DOI: 10.3892/etm.2017.4730.

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