Hmsn-P Caused by P.Pro285leu Mutation in Tfg Is Not Confined to Patients With Far East Ancestry Publisher Pubmed



Alavi A¹ ; Shamshiri H² ; Nafissi S² ; Khani M¹ ; Klotzle B³ ; Fan JB³ ; Steemers F³ ; Elahi E^{1, 4} Show Affiliations
Source: Neurobiology of Aging Published:2015

Abstract

Hereditary motor and sensory neuropathy with proximal predominance (HMSN-P) is a rare disease so far identified only in individuals of Far East ancestry. Here, genome-wide linkage analysis and exome sequencing in an Iranian pedigree with 16 members affected with a neuromuscular disease led to identification of a mutation in TFG that causes p.Pro285Leu as cause of disease. The very same mutation was reported as cause of HMSN-P during the course of the study. Phenotypic analysis in conjunction with genetic data revealed that the Iranian patients were also affected with HMSN-P. Therefore, HMSN-P is not confined to the Far East and may simply not have been diagnosed in other populations. Haplotype analysis suggests at least 3 independent origins for mutated alleles that cause p.Pro285Leu. The phenotypic data gathered included subjective, biochemical, nerve conduction, electromyography, and muscle magnetic resonance imaging data. Comparison with patients with same disease in previous publications showed that clinical variability exists, sensory nerves are prominently affected, and proximal and distal muscles are involved. © 2015 Elsevier Inc.