Hereditary inclusion body myopathy: the Middle Eastern genetic cluster.
BACKGROUND
Recessively inherited hereditary inclusion body myopathy (HIBM) with quadriceps sparing was initially described only in Jews originating from the region of Persia. The recent identification of the gene responsible for this myopathy and the common "Persian Jewish mutation" (M712T) enabled the re-evaluation of atypical phenotypes and the epidemiology of HIBM in various communities in the Middle East.


OBJECTIVE
To test for the M712T mutation in the DNA from HIBM patients in the Middle East.


METHODS
DNA from all suspected HIBM patients was tested for the M712T mutation. Unaffected members of families with genetically proven HIBM were studied too. In the majority of families, haplotype construction with markers spanning the 700-kb region of the HIBM gene was performed.


RESULTS
One hundred twenty-nine HIBM patients of 55 families (Middle Eastern Jews, Karaites, and Arab Muslims of Palestinian and Bedouin origin) were homozygous for the M712T mutation, and all carried the same haplotype. Five clinically unaffected subjects were also homozygous for the common mutation and haplotype, including two older adults (ages 50 and 68 years). Atypical features with this same mutation were marked quadriceps weakness in five patients, proximal weakness only in two patients, facial weakness in three patients, and a muscle biopsy showing perivascular inflammation in one patient.


CONCLUSIONS
The phenotypic spectrum of recessive HIBM is wider than previously described, and the diagnostic criteria for this myopathy must be changed. The Middle Eastern cluster is the result of a founder mutation, with incomplete penetrance, that is approximately 1,300 years old and is not limited to Jews.
Department of Neurology and Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital and Hebrew University-Hadassah Medical School, Jerusalem. zargov@md2.huji.ac.il
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Argov
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Eisenberg
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Grabov-Nardini
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Sadeh
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Wirguin
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Soffer
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Mitrani-Rosenbaum
D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D018912:Arabs / Q000235:genetics; D002238:Carbohydrate Epimerases / Q000172:deficiency / Q000235:genetics; D005260:Female; D018703:Founder Effect; D005808:Genes, Recessive; D005838:Genotype; D006239:Haplotypes; D049690:History, Ancient; D006801:Humans; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008877:Middle East / Q000208:ethnology; D020125:Mutation, Missense; D018979:Myositis, Inclusion Body / Q000208:ethnology / Q000235:genetics* / Q000266:history; D010641:Phenotype; D017354:Point Mutation
D002238:Carbohydrate Epimerases; C100033:UDP acetylglucosamine-2-epimerase