Abstract
Usher syndrome type 1 describes the association of profound, congenital
sensorineural deafness, vestibular hypofunction and childhood onset retinitis
pigmentosa. It is an autosomal recessive condition and is subdivided
on the basis of linkage analysis into types 1A through 1E (refs
2–6). Usher type 1C maps to the region containing the genes
ABCC8 and KCNJ11 (encoding components of ATP-sensitive K
+ (KATP) channels), which may be mutated in patients with hyperinsulinism. We identified three individuals from two consanguineous
families with severe hyperinsulinism, profound congenital sensorineural deafness,
enteropathy and renal tubular dysfunction. The molecular basis of the disorder
is a homozygous 122-kb deletion of 11p14–15, which includes part of
ABCC8 and overlaps with the locus for Usher syndrome type 1C and DFNB18
(ref. 11). The centromeric boundary of this deletion
includes part of a gene shown to be mutated in families with type 1C Usher
syndrome, and is hence assigned the name USH1C. The pattern of expression
of the USH1C protein is consistent with the clinical features exhibited by
individuals with the contiguous gene deletion and with isolated Usher type
1C.
