title: Infantile hyperinsulinism associated with enteropathy, deafness and renal tubulopathy: clinical manifestations of a syndrome caused by a contiguous gene deletion located on chromosome 11p.
abstract: We describe the clinical features of a new syndrome causing hyperinsulinism in infancy (HI), severe enteropathy, profound sensorineural deafness, and renal tubulopathy in three children born to two pairs of consanguineous parents. This combination of clinical features is explained by a 122-kb contiguous gene deletion on the short arm of chromosome 11. It deletes 22 of the 39 exons of the gene coding for the SUR1 component of the KATP channel on the pancreatic beta-cell thereby causing severe HI. It also deletes all but two of the 28 exons of the USH1C gene, which causes Usher syndrome and is important for the normal development and function of the ear and the eye, the gastrointestinal tract, and the kidney, thereby accounting for the symptoms of deafness, vestibular dysfunction and retinal dystrophy seen in type 1 Usher syndrome, diarrhoea, malabsorption, and tubulopathy. This contiguous gene deletion provides important insights into the normal development of several body organ systems.
authors.affiliation: London Centre for Paediatric Endocrinology and Metabolism, Great Ormond Street Hospital for Children NHS Trust and Institute of Child Health, London, UK. K.Hussain@ich.ucl.ac.uk
authors.forename: Khalid
authors.initials: K
authors.lastname: Hussain
authors.forename: Maria
authors.initials: M
authors.lastname: Bitner-Glindzicz
authors.forename: Diana
authors.initials: D
authors.lastname: Blaydon
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Lindley
authors.forename: Dorothy A
authors.initials: DA
authors.lastname: Thompson
authors.forename: Tony
authors.initials: T
authors.lastname: Kriss
authors.forename: Kaukat
authors.initials: K
authors.lastname: Rajput
authors.forename: Dina G
authors.initials: DG
authors.lastname: Ramadan
authors.forename: Z
authors.initials: Z
authors.lastname: Al-Mazidi
authors.forename: Karen E
authors.initials: KE
authors.lastname: Cosgrove
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Dunne
authors.forename: Albert
authors.initials: A
authors.lastname: Aynsley-Green
mesh_terms: D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11; D003638:Deafness / Q000150:complications* / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D006946:Hyperinsulinism / Q000150:complications* / Q000235:genetics; D007223:Infant; D007410:Intestinal Diseases / Q000150:complications* / Q000235:genetics; D007684:Kidney Tubules / Q000473:pathology*; D013577:Syndrome