Argov and Yarom (1984) described the disorder in Jews of Persian origin. The onset of this disorder usually occurred after the age of 20 years but before the middle of the fourth decade of life. Proximal and distal ... Argov and Yarom (1984) described the disorder in Jews of Persian origin. The onset of this disorder usually occurred after the age of 20 years but before the middle of the fourth decade of life. Proximal and distal muscle weakness and wasting of the upper and lower limbs were progressive and resulted in severe incapacitation within 10 to 20 years. Despite this, there typically was sparing of the quadriceps muscles even in advanced stages of the disease, a feature unique to this form of inclusion body myopathy. It was not clear to the authors whether this disorder was primarily neurogenic or myopathic. Massa et al. (1991) reported 2 unrelated patients, each from a family of Iranian-Kurdish-Jewish origin. The picture was that of adult-onset, slowly progressive limb-girdle muscle weakness with a remarkable sparing of quadriceps muscles. Zlotogora (1995) reported that this condition had been identified in 19 subjects of Iranian Jewish extraction and 3 others, possibly of that origin. They cited the reports of Adam et al. (1981), Argov and Yarom (1984), and Sadeh et al. (1993). Muscular weakness usually appeared in the third decade as gait difficulties. Progression was gradual, and most patients became severely incapacitated a decade after onset. Ocular, pharyngeal, and cardiac muscles were not involved. The muscles of the shoulder girdle were severely affected in advanced cases, with relative sparing of the deltoid, biceps, and triceps. In the lower limbs, foot dorsiflexion was usually very weak at an early stage of the disease. When leg muscle weakness becomes widespread, the most characteristic finding becomes evident, namely sparing of the quadriceps. The quadriceps muscles stayed strong even in advanced stages of the disorder, and thus the patients were able to stand and walk until late in the course of the disease. Creatine kinase levels were normal or moderately elevated, and nerve conduction velocity was normal.
Sivakumar et al. (1995) analyzed the sequence of exons 16 and 17 of amyloid precursor protein in 8 individuals with familial inclusion body myopathy, including 5 patients from Caucasian families segregating IBM in autosomal dominant fashion and 3 ... Sivakumar et al. (1995) analyzed the sequence of exons 16 and 17 of amyloid precursor protein in 8 individuals with familial inclusion body myopathy, including 5 patients from Caucasian families segregating IBM in autosomal dominant fashion and 3 individuals who had apparent autosomal recessive inheritance, 1 of whom was of Iranian-Jewish ancestry. No mutations were demonstrated in these exons. After excluding other potential candidate genes that mapped to the region, Eisenberg et al. (2001) identified mutations in the GNE gene (603824) in affected members of the QSM families: all patients of Middle Eastern descent shared a single homozygous missense mutation (603824.0005), whereas affected individuals of families of other ethnic origins were compound heterozygotes for distinct mutations. In 2 second cousins from an Italian family with IBM2, Broccolini et al. (2002) identified compound heterozygosity in the GNE gene: a novel mutation (met171 to val; 603824.0016) and M712T (603824.0005). The authors noted that it was the first report of the M712T mutation in patients of non-Middle Eastern descent. In an American patient with IBM2, Vasconcelos et al. (2002) identified compound heterozygosity in the GNE gene, expanding the genetic heterogeneity of the disorder.
This disorder, affecting mainly leg muscles but with an unusual distribution that spares the quadriceps, was first described in Jews of Persian descent (Argov and Yarom, 1984). It was later found in Jews originating from other Middle Eastern ... This disorder, affecting mainly leg muscles but with an unusual distribution that spares the quadriceps, was first described in Jews of Persian descent (Argov and Yarom, 1984). It was later found in Jews originating from other Middle Eastern countries, as well as in non-Jews. Argov et al. (2003) identified homozygosity for the GNE M712T mutation (603824.0005) in 129 Middle Eastern patients with IBM2 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 IBM2 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.