title: Prevalence of GNE p.M712T and hereditary inclusion body myopathy (HIBM) in Sangesar population of Northern Iran.
abstract: GNE myopathy or hereditary inclusion body myopathy (HIBM) is an ultra-rare severely disabling autosomal recessive adult onset muscle disease which affects roughly one to three individuals per million worldwide. Genetically, HIBM is caused by mutations in the glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase gene (GNE), resulting in diminished enzyme function and reduced sialic acid biosynthesis. A founder variant GNE p.M712T was first described in patients of Iranian and Middle-Eastern descent living outside of Iran. Asymptomatic heterozygote or carrier frequency has been reported as high as 1 in 11 within the Persian-Jewish community residing in Los Angeles, CA. To investigate the prevalence of the p.M712T variant in Iran, we studied 792 samples collected from random individuals in Sangesar (Mahdishahr) in Northern Iran. DNA samples were obtained by buccal swab, and genotyping was performed by melting curve analysis. The results included 31 of 792 (3.91%) heterozygous carriers and 5 (0.31%) homozygotes for GNE p.M712T. All five homozygous individuals, age 30-64 years, were already symptomatic at the start of the study. Our findings suggest that the prevalence of GNE p.M712T is higher in the Sangesar population, comprised mostly of Muslim and Bahai descendants, compared with the general world population. Additional HIBM distribution studies are warranted within various subpopulations of Iran.
authors.affiliation: HIBM Research Group, Reseda, CA, USA; Sangesar Charity Organization for HIBM, Sangesar, Semnan, Iran.
authors.forename: H
authors.initials: H
authors.lastname: Khademian
authors.forename: E
authors.initials: E
authors.lastname: Mehravar
authors.forename: Ja
authors.initials: J
authors.lastname: Urtizberea
authors.forename: S
authors.initials: S
authors.lastname: Sagoo
authors.forename: L
authors.initials: L
authors.lastname: Sandoval
authors.forename: R
authors.initials: R
authors.lastname: Carbajo
authors.forename: B
authors.initials: B
authors.lastname: Darvish
authors.forename: Y
authors.initials: Y
authors.lastname: Valles-Ayoub
authors.forename: D
authors.initials: D
authors.lastname: Darvish
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D049310:Distal Myopathies / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005838:Genotype; D005843:Geography; D006801:Humans; D007223:Infant; D007492:Iran / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D015995:Prevalence; D055815:Young Adult
chemical_list: D009097:Multienzyme Complexes; C482901:UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase
keywords: IBM2; Nonaka myopathy; Persia; Persian; disability; distal myopathy with rimmed vacuoles; dystrophy; epidemiology; muscle; orphan disease; quadriceps sparing myopathy; rare disease; sialic