In 8 Libyan Jewish families with limb-girdle muscular dystrophy type 2B (LGMDR2; 253601), Bashir et al. (1998) found that affected individuals were homozygous for a 1-bp deletion of guanine and a C-G transversion at codon 1322 of the DYSF gene, resulting in a frameshift and premature stop codon at position 1331 (numbering based on a partial DYSF amino acid sequence). Subsequently, Therrien et al. (2006) reported the mutation as an insertion/deletion (4872delinsCCCC). In a ninth Libyan Jewish family, with a single affected member, the mutation was detected in single copy; one of the parents (who did not carry the mutation) was of Romanian origin. The 25 patients in these families showed onset of the disease between 12 and 39 years of age (mean 19.5 +/- 5 years). All had lower limb involvement on average 9 years before upper limb symptoms. Thirteen patients (52%) presented with distal lower limb muscle weakness, mostly of the gastrocnemius, with some complaining of transient calf enlargement. Intrafamilial variability was seen in the distribution of muscle weakness. Only 6 patients had lost the ability to walk independently; all of these were older than 35 years. Muscle biopsy showed chronic myopathic changes, and creatine kinase was elevated 10 to 25 times the normal rate in all affected individuals.
In 2 Italian sisters with severe LGMDR2, Sinnreich et al. (2006) identified homozygosity for the insertion/deletion mutation in the DYSF gene, which they characterized as a 1-bp deletion (4872delG) and a 4876G-C transversion, that was previously reported by Bashir et al. (1998). Each parent was heterozygous for the insertion/deletion mutation. The girls had onset in the second decade of proximal muscle weakness and wasting. Their 70-year-old mother, who had had mild proximal weakness since her forties, was compound heterozygous for the indel mutation and a splice site mutation (603009.0016).
