title: Three novel mutations in the ANK membrane protein cause craniometaphyseal dysplasia with variable conductive hearing loss.
abstract: Craniometaphyseal dysplasia (CMD) is a rare, sclerosing skeletal disorder caused by mutations in ANKH, which encodes a putative pyrophosphate transporting membrane protein. Six distinct ANKH mutations have been described to date. We report here on three novel mutations in simplex patients with CMD. The c.1015T>C (p.Cys339Arg) mutation found in Patient A was associated with congenital facial palsy, early-onset conductive hearing loss, and a generalized undermodeling of the long bones. The c.1172T>C (p.Leu391Pro) mutation in Patient B was associated with facial palsy, progressive conductive hearing loss, and generalized undermodeling of tubular bones. A milder phenotype without cranial nerve affection was observed in Patient C, associated with a c.1001T>G (p.Leu334Arg) mutation. All affected residues lie in evolutionarily conserved sequence blocks. These additional cases and the associated mutations contribute to an improved appreciation of the variability of this rare skeletal dysplasia. (c) 2010 Wiley-Liss, Inc.
authors.affiliation: Institute of Medical Genetics, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Kornak
authors.forename: Francesco
authors.initials: F
authors.lastname: Brancati
authors.forename: Martine
authors.initials: M
authors.lastname: Le Merrer
authors.forename: Klaske
authors.initials: K
authors.lastname: Lichtenbelt
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Höhne
authors.forename: Sigrid
authors.initials: S
authors.lastname: Tinschert
authors.forename: Francesco Giuseppe
authors.initials: FG
authors.lastname: Garaci
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001848:Bone Diseases, Developmental / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006314:Hearing Loss, Conductive / Q000150:complications* / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D028061:Phosphate Transport Proteins / Q000737:chemistry / Q000235:genetics*; D011247:Pregnancy; D012598:Sclerosis; D012886:Skull / Q000000981:diagnostic imaging / Q000473:pathology; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: C498770:ANKH protein, human; D008565:Membrane Proteins; D028061:Phosphate Transport Proteins