Novel homozygous missense mutation in GAN associated with Charcot-Marie-Tooth disease type 2 in a large consanguineous family from Israel

BMC Medical Genetics

Research Article

Rachel Straussberg¹  Yoram Nevo¹  Sharon Aharoni¹  Meriel M. McEntagart²  Michael Weedon³  Katy E. S. Barwick⁴  Gaurav V. Harlalka⁴  Barry A. Chioza⁴  Andrew H. Crosby⁴  Aviva Mimouni-Bloch⁵ 

[1] Department of Neurology, Schneider Children’s Medical Center of Israel, Petach Tikva, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;Medical Genetics Unit, Floor 0, Jenner Wing, St. George’s University of London, Cranmer Terrace, SW17 0RE, London, UK;Medical Research, Diabetes group, RILD Wellcome Wolfson Centre (Level 3), Royal Devon and Exeter NHS Foundation Trust, EX2 5DW, Exeter, Devon, UK;Medical Research, RILD Wellcome Wolfson Centre (Level 4), Royal Devon and Exeter NHS Foundation Trust, EX2 5DW, Exeter, Devon, UK;The Pediatric Neurology and Developmental Unit, Loewenstein Rehabilitation Hospital, Raanana, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;

关键词: GAN;    Charcot-Marie-Tooth disease type 2;    Giant axonal neuropathy;   

DOI  :  10.1186/s12881-016-0343-x

 received in 2016-06-10, accepted in 2016-11-07,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundCMT-2 is a clinically and genetically heterogeneous group of peripheral axonal neuropathies characterized by slowly progressive weakness and atrophy of distal limb muscles resulting from length-dependent motor and sensory neurodegeneration. Classical giant axonal neuropathy (GAN) is an autosomal recessively inherited progressive neurodegenerative disorder of the peripheral and central nervous systems, typically diagnosed in early childhood and resulting in death by the end of the third decade. Distinctive phenotypic features are the presence of “kinky” hair and long eyelashes. The genetic basis of the disease has been well established, with over 40 associated mutations identified in the gene GAN, encoding the BTB-KELCH protein gigaxonin, involved in intermediate filament regulation.MethodsAn Illumina Human CytoSNP-12 array followed by whole exome sequence analysis was used to identify the disease associated gene mutation in a large consanguineous family diagnosed with Charcot-Marie-Tooth disease type 2 (CMT-2) from which all but one affected member had straight hair.ResultsHere we report the identification of a novel GAN missense mutation underlying the CMT-2 phenotype observed in this family. Although milder forms of GAN, with and without the presence of kinky hair have been reported previously, a phenotype distinct from that was investigated in this study. All family members lacked common features of GAN, including ataxia, nystagmus, intellectual disability, seizures, and central nervous system involvement.ConclusionsOur findings broaden the spectrum of phenotypes associated with GAN mutations and emphasize a need to proceed with caution when providing families with diagnostic or prognostic information based on either clinical or genetic findings alone.

【 授权许可】

CC BY   
© The Author(s). 2016