Three novel mutations in the ANK membrane protein cause craniometaphyseal dysplasia with variable conductive hearing loss

Uwe Kornak, Francesco Brancati, Martine Le Merrer, Klaske Lichtenbelt, Wolfgang Höhne, Sigrid Tinschert, Francesco Giuseppe Garaci, Bruno Dallapiccola, Peter Nürnberg

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)870-874
Number of pages5
JournalAmerican Journal of Medical Genetics, Part A
Volume152
Issue number4
DOIs
Publication statusPublished - Apr 2010

Fingerprint

Conductive Hearing Loss
Membrane Proteins
Mutation
Facial Paralysis
Bone and Bones
Cranial Nerves
Conserved Sequence
Schwartz-Lelek syndrome
Phenotype

Keywords

  • ANKH
  • Clinical variability
  • Craniometaphyseal dysplasia
  • Novel mutations

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Three novel mutations in the ANK membrane protein cause craniometaphyseal dysplasia with variable conductive hearing loss. / Kornak, Uwe; Brancati, Francesco; Le Merrer, Martine; Lichtenbelt, Klaske; Höhne, Wolfgang; Tinschert, Sigrid; Garaci, Francesco Giuseppe; Dallapiccola, Bruno; Nürnberg, Peter.

In: American Journal of Medical Genetics, Part A, Vol. 152, No. 4, 04.2010, p. 870-874.

Research output: Contribution to journalArticle

Kornak, Uwe ; Brancati, Francesco ; Le Merrer, Martine ; Lichtenbelt, Klaske ; Höhne, Wolfgang ; Tinschert, Sigrid ; Garaci, Francesco Giuseppe ; Dallapiccola, Bruno ; Nürnberg, Peter. / Three novel mutations in the ANK membrane protein cause craniometaphyseal dysplasia with variable conductive hearing loss. In: American Journal of Medical Genetics, Part A. 2010 ; Vol. 152, No. 4. pp. 870-874.
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