A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene

Usher syndrome type 1 describes the association of profound, congenital sen sorineural deafness, vestibular hypofunction and childhood onset retinitis pigmentosa(1). It is an autosomal recessive condition and is subdivided on the basis of linkage analysis into types 1A through 1E (refs 2-6), Usher ty pe 1C maps to the region containing the genes ABCC8 and KCNJ11 (encoding co mponents of ATP-sensitive K+ (KATP) channels), which may be mutated in pati ents with hyperinsulinism(7-10). We identified three individuals from two c onsanguineous families with severe hyperinsulinism, profound congenital sen sorineural deafness, enteropathy and renal tubular dysfunction. The molecul ar 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 include s part of a gene shown to be mutated in families with type 1C Usher syndrom e, and is hence assigned the name USH1C. The pattern of expression of the U SH1C protein is consistent with the clinical features exhibited by individu als with the contiguous gene deletion and with isolated Usher type 1C.