A start codon mutation of the FRMD7 gene in two Korean families with idiopathic infantile nystagmus.

Jae-Hwan Choi,Jae-Ho Jung,Je Hyun Seo,Kwang-Dong Choi,Jin-Hong Shin

doi:10.1038/srep13003

Jae-Hwan Choi, Jae-Ho Jung + Show 3 more

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https://doi.org/10.1038/srep13003

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Abstract

Idiopathic infantile nystagmus (IIN) is the involuntary oscillation of the eyes with onset in the first few months of life. The most common form of inheritance is X-linked, and mutations in FRMD7 gene are a major cause. To identify the FRMD7 gene mutations associated with X-linked IIN, we performed PCR-based DNA direct sequencing in 4 affected subjects from 2 Korean families. We also assessed structural abnormalities of retina and optic nerve head using optical coherence tomography (OCT). Genetic analysis revealed a A>G transversion at nucleotide c.1, the first base of the start codon. This mutation leads to the loss of the primary start codon ATG for methionine, which is replaced by a triplet GTG for valine. The alternative in-frame start codon is not present around a mutation. OCT revealed the morphological changes within the optic nerve head, including shallow cup depth and small cup-to-disc ratio. In summary, we identified a novel start codon mutation within the FRMD7 gene of 2 Korean families. Our data expands the mutation spectrum of FRMD7 causing IIN. We also demonstrated abnormal developments of afferent system in patients with FRMD7 mutations using OCT, which may help to understand the etiological factor in development of nystagmus.

Highlights

Idiopathic infantile nystagmus (IIN) is the involuntary oscillation of the eyes with onset in the first few months of life[1]
Many mutations within FRMD7 gene have been reported in IIN patients, and discovery of gene mutations has led to understand the etiology of IIN at a cellular level
FRMD7 expression studies using in situ hybridization showed restricted expressions within the developing afferent and efferent arms of vestibule-ocular and optokinetic reflex, the developing cerebellum and neural integrator site[5,9]

Summary

Introduction

Idiopathic infantile nystagmus (IIN) is the involuntary oscillation of the eyes with onset in the first few months of life[1]. IIN usually develops independently of any other ocular diseases such as albinism, achromatopsia or Leber congenital amaurosis. Many hypotheses have been proposed to explain the mechanism of IIN, including miswiring of retinal ganglion cells[2], the instability of the neural integrator[3] or disrupted development of a dual pursuit/motion tracking systems[4]. IIN may be inherited as an autosomal dominant, autosomal recessive or X-linked trait. The most common form of inheritance is X-linked, which can be either dominant or recessive. In situ hybridization studies showed restricted FRMD7 expressions in the developing vestibulo-ocular www.nature.com/scientificreports/. Optical coherence tomography (OCT) study revealed abnormal developments of retina and optic nerve in patients with FRMD7 mutations[10]. We report a common start codon mutation of FRMD7 gene in 2 Korean families. We assessed structural abnormalities of retina and optic nerve head using OCT

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