A founder mutation in XXXX is a major cause of @entity17325 .

@entity1 @entity2057 @entity29731 @entity908 @entity3986 @entity425 @entity73291 @entity460 @entity2865 @entity21280 @entity6191 @entity17325
The @entity17325 are a group of disorders with wide genetic and clinical heterogeneity. Recently, mutations in the @entity21280 gene, which encodes a putative @entity460 -activated @entity2865 channel belonging to the Anoctamin family of proteins, were identified in five families with one of two previously identified disorders, @entity17325 2L and @entity3986 . We screened a candidate group of 64 @entity1 from 59 British and German kindreds and found the truncating mutation, @entity73291 in exon 5 of @entity21280 in 20 @entity1 , homozygously in 15 and in compound heterozygosity with other @entity21280 variants in the rest. An intragenic single nucleotide polymorphism and an extragenic microsatellite marker are in linkage disequilibrium with the mutation, suggesting a founder effect in the Northern European population. We have further defined the clinical phenotype of @entity21280 -associated @entity3986 . @entity1 show adult onset proximal lower limb @entity425 with highly raised serum @entity908 kinase values (average 4500 IU/l) and frequent @entity2057 and asymmetry of muscle involvement. Onset varies from the early 20 s to 50 s and the @entity425 is @entity6191 progressive, with most @entity1 remaining ambulant for several decades. Distal presentation is much less common but a milder degree of distal lower limb @entity425 is often observed. Upper limb strength is only mildly affected and cardiac and respiratory function is normal. Females appear less frequently affected. In the North of England population we have identified eight @entity1 with @entity21280 mutations, suggesting a minimum prevalence of 0.27/100,000, twice as common as @entity29731 . We suggest that mutations in @entity21280 represent a relatively common cause of adult onset @entity3986 with high serum @entity908 kinase and that mutation screening, particularly of the common mutation @entity73291 , should be an early step in the diagnostic algorithm of adult @entity17325 @entity1 .
