title: A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene.
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. 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. 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.
authors.affiliation: Department of Clinical and Molecular Genetics, Institute of Child Health, and Great Ormond Street Hospital for Children NHS Trust, London, UK. mbitnerg@ich.ucl.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Bitner-Glindzicz
authors.forename: K J
authors.initials: KJ
authors.lastname: Lindley
authors.forename: P
authors.initials: P
authors.lastname: Rutland
authors.forename: D
authors.initials: D
authors.lastname: Blaydon
authors.forename: V V
authors.initials: VV
authors.lastname: Smith
authors.forename: P J
authors.initials: PJ
authors.lastname: Milla
authors.forename: K
authors.initials: K
authors.lastname: Hussain
authors.forename: J
authors.initials: J
authors.lastname: Furth-Lavi
authors.forename: K E
authors.initials: KE
authors.lastname: Cosgrove
authors.forename: R M
authors.initials: RM
authors.lastname: Shepherd
authors.forename: P D
authors.initials: PD
authors.lastname: Barnes
authors.forename: R E
authors.initials: RE
authors.lastname: O'Brien
authors.forename: P A
authors.initials: PA
authors.lastname: Farndon
authors.forename: J
authors.initials: J
authors.lastname: Sowden
authors.forename: X Z
authors.initials: XZ
authors.lastname: Liu
authors.forename: M J
authors.initials: MJ
authors.lastname: Scanlan
authors.forename: S
authors.initials: S
authors.lastname: Malcolm
authors.forename: M J
authors.initials: MJ
authors.lastname: Dunne
authors.forename: A
authors.initials: A
authors.lastname: Aynsley-Green
authors.forename: B
authors.initials: B
authors.lastname: Glaser
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D018797:Cell Cycle Proteins; D002460:Cell Line; D002675:Child, Preschool; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11; D003241:Consanguinity; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D004386:Duodenum / Q000378:metabolism; D005091:Exons; D005123:Eye / Q000196:embryology; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D005808:Genes, Recessive; D008040:Genetic Linkage; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D006946:Hyperinsulinism / Q000235:genetics*; D007150:Immunohistochemistry; D007223:Infant; D007438:Introns; D007473:Ion Channels / Q000235:genetics; D007684:Kidney Tubules / Q000002:abnormalities; D008297:Male; D008969:Molecular Sequence Data; D010179:Pancreas / Q000002:abnormalities; D010375:Pedigree; D012326:RNA Splicing / Q000235:genetics; D012160:Retina / Q000196:embryology; D012162:Retinal Degeneration / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016324:Sequence Tagged Sites
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D007473:Ion Channels; C118970:USH1C protein, human