FRMD7相关先天性眼球震颤的临床和分子学发现作为眼白化病的鉴别诊断

Clinical and molecular findings of FRMD7 related congenital nystagmus as adifferential diagnosis of ocular albinism.

作者信息

Michaud Vincent, Defoort-Dhellemmes Sabine, Drumare Isabelle, Pennamen Perrine, Plaisant Claudio, Lasseaux Eulalie, Arveiler Benoit

机构信息

a Service de Génétique Médicale , CHU de Bordeaux , Bordeaux , France.

b Service d'exploration de la vision et neuro-ophtalmologie , CHRU de Lille , Lille , France.

出版信息

Ophthalmic Genet. 2019 Apr;40(2):161-164. doi: 10.1080/13816810.2019.1592201. Epub 2019 Apr 3.

DOI:10.1080/13816810.2019.1592201

PMID:30942644

Abstract

BACKGROUND

Congenital nystagmus is one of the most common neuro-ophthalmological disorders. X chromosome-linked forms are associated with pathogenic variants of the GPR143 and FRMD7 genes.

MATERIALS AND METHODS

Patients' DNA was analyzed using a next-generation sequencing (NGS) panel of genes involved in albinism and related pathologies (TYR, OCA2, TYRP1, SLC45A2, SLC24A5, C10ORF11, GPR143, SLC38A8, HPS 1 to 10, LYST, MITF, FRMD7) Results: We report a 4 generation family with 5 affected members initially referred for molecular diagnosis of ocular albinism. A missense variant of FRMD7 was found in 3 affected cases and one female carrier. We show that the disease in the affected girl is due to skewed inactivation of the X chromosome.

CONCLUSIONS

By compiling all the published cases we discuss the variable penetrance among females due to different types of mutation and to X-inactivation.

摘要

背景

先天性眼球震颤是最常见的神经眼科疾病之一。X染色体连锁型与GPR143和FRMD7基因的致病变异有关。

材料与方法

使用涉及白化病及相关病症的基因二代测序（NGS） panel（TYR、OCA2、TYRP1、SLC45A2、SLC24A5、C10ORF11、GPR143、SLC38A8、HPS 1至10、LYST、MITF、FRMD7）对患者DNA进行分析。结果：我们报告了一个有5名受累成员的四代家族，最初因眼部白化病的分子诊断前来就诊。在3例受累病例和1名女性携带者中发现了FRMD7的错义变异。我们表明，受累女孩的疾病是由于X染色体的偏态失活。