ClinVar Genomic variation as it relates to human health

In 47 Middle Eastern Jewish families, Eisenberg et al. (2001) found that affected individuals with Nonaka myopathy (NM; 605820), which the authors called hereditary inclusion body myopathy (HIBM), had a 2186T-C transition in exon 12 of the GNE gene, resulting in a met712-to-thr (M712T) amino acid change in the kinase domain of the protein. In 2 second cousins from an Italian family diagnosed with HIBM, Broccolini et al. (2002) identified compound heterozygosity for mutations in the GNE gene: M712T and a novel mutation (M171V; 603824.0016). The authors noted that it was the first report of the M712T mutation in patients of non-Middle Eastern descent. Argov et al. (2003) identified homozygosity for the M712T mutation in 129 Middle Eastern patients diagnosed with HIBM from 55 families. Eleven patients had atypical features: 5 had involvement of the quadriceps muscle, 2 patients did not have distal weakness, 3 patients had facial weakness, and 1 patient had perivascular inflammation. There were 5 unaffected individuals with the homozygous mutation from 5 different HIBM families, including 2 who were 50 and 68 years old. The families included Middle Eastern Jews, Karaites, and Arab Muslims of Palestinian and Bedouin origin. Argov et al. (2003) offered a detailed historical perspective of the different cultures, and concluded that this founder mutation is approximately 1,300 years old and is not limited to those of Jewish descent. In a Japanese patient with Nonaka myopathy, Tomimitsu et al. (2004) identified compound heterozygosity for the M712T mutation and the A631V mutation (603824.0015). The findings indicated that Nonaka myopathy and what was previously called hereditary inclusion body myopathy are identical disorders. (less)