HMSN-P caused by p.Pro285Leu mutation in TFG is not confined to patients with Far East ancestry.
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.
School of Biology, College of Science, University of Tehran, Tehran, Iran.
Afagh
A
Alavi
Department of Neurology, Tehran University of Medical Sciences, Tehran, Iran.
Hosein
H
Shamshiri
Department of Neurology, Tehran University of Medical Sciences, Tehran, Iran.
Shahriar
S
Nafissi
School of Biology, College of Science, University of Tehran, Tehran, Iran.
Marzieh
M
Khani
Illumina, San Diego, CA, USA.
Brandy
B
Klotzle
Illumina, San Diego, CA, USA.
Jian-Bing
JB
Fan
Illumina, San Diego, CA, USA.
Frank
F
Steemers
School of Biology, College of Science, University of Tehran, Tehran, Iran; Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran. Electronic address: elahe.elahi@gmail.com.
Elahe
E
Elahi
D000328:Adult; D000368:Aged; D000483:Alleles; D059472:Exome / Q000235:genetics; D005202:Asia, Eastern; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006239:Haplotypes; D015417:Hereditary Sensory and Motor Neuropathy / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007492:Iran; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D033921:Vesicular Transport Proteins
D011506:Proteins; C096163:TFG protein, human; D033921:Vesicular Transport Proteins
HMSN-P; Haplotypes; TFG; p.Pro285Leu