The numbering of this CAV3 mutation (C72W) is based on the numbering system used by Fulizio et al. (2005). Early reports designated this mutation CYS71TRP.
In 1 of 82 patients with muscular dystrophy, McNally et al. (1998) identified a heterozygous C-to-G change in the CAV3 gene, resulting in a cys71-to-trp (C71W) substitution. The patient had progressive proximal muscle weakness beginning in the first decade, but remained ambulatory in the mid-second decade. Her mother and 2 siblings had the identical missense change, but did not have symptoms of muscular dystrophy, suggesting that a single abnormal allele is not sufficient to cause the phenotype and that the likely inheritance is autosomal recessive. The authors were unable to determine the nature of the second allele in the proband. The mutation was not identified in 200 control chromosomes. McNally (1998) suspected that the phenotype was the result of either loss-of-function mutations or dominant-negative mutations; she doubted that haploinsufficiency leads to the disease. The family was lost to follow-up.
Among 100 normal Brazilian control subjects without LGMD, de Paula et al. (2001) identified heterozygosity for the C71W change in 1 subject. They concluded that C71W is a rare polymorphism that does not cause an abnormal phenotype when present in just one allele.
