Reply: Early-onset Behr syndrome due to compound heterozygous mutations in OPA1

Patrick Yu-Wai-Man,Patrick F Chinnery

doi:10.1093/brain/awu187

Abstract

Reply: Early-onset Behr syndrome due to compound heterozygous mutations in OPA1

Highlights

dominant optic atrophy (DOA) was largely viewed as a limited genetic disorder that preferentially affects retinal ganglion cells resulting in progressive visual failure from early childhood (Carelli et al, 2004; Yu-Wai-Man et al, 2014)
In a large multicentre study published in Brain, up to 20% of OPA1 mutation carriers developed these so-called DOA plus (DOA + ) phenotypes where the optic atrophy was complicated by a wide range of neuromuscular features that included ataxia, myopathy, peripheral neuropathy, sensorineural deafness, and fascinatingly, chronic progressive external ophthalmoplegia (YuWai-Man et al, 2010)
Bonneau and colleagues extend the association between pathogenic OPA1 mutations and Behr’s syndrome with a detailed account of four unrelated children who developed the typical clinical features of an early-onset progressive optic neuropathy that was further compounded by ataxia, spasticity and peripheral neuropathy (Bonneau et al, 2014). Their most striking observation is the identification of compound heterozygous OPA1 mutations in all four patients with the co-occurrence of a missense GTPase mutation and a truncative nonsense mutation. Three of these families harboured the same missense GTPase OPA1 mutation (c.1146A4G, p.Ile382Met) that has been previously reported in another DOA+ family with compound heterozygous mutations (Schaaf et al, 2011)

Summary

Introduction

Correspondence to: Dr Patrick Yu-Wai-Man, Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK E-mail: Patrick.Yu-Wai-Man@ncl.ac.uk Autosomal dominant optic atrophy (DOA) is the most commonly diagnosed inherited optic neuropathy in clinical practice and the majority of patients harbour pathogenic mutations within the OPA1 gene (3q28-q29, OMIM 165500) (Yu-Wai-Man and Chinnery, 2013).

Results

Conclusion