| Twenty-five novel mutations including duplications in the ATP7A gene. | |
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MedLine Citation:
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PMID: 21208200 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Moizard M-P, Ronce N, Blesson S, Bieth E, Burglen L, Mignot C, Mortemousque I, Marmin N, Dessay B, Danesino C, Feillet F, Castelnau P, Toutain A, Moraine C, Raynaud M. Twenty-five novel mutations including duplications in the ATP7A gene. Menkes disease (MD) and occipital horn syndrome (OHS) are allelic X-linked recessive copper deficiency disorders resulting from ATP7A gene mutations. MD is a severe condition leading to progressive neurological degeneration and death in early childhood, whereas OHS has a milder phenotype with mainly connective tissue abnormalities. Until now, molecular analyses have revealed only deletions and point mutations in both diseases. This study reports new molecular data in a series of 40 patients referred for either MD or OHS. We describe 23 point mutations (9 missense mutations, 7 splice site variants, 4 nonsense mutations, and 3 small insertions or deletions) and 7 intragenic deletions. Of these, 18 point mutations and 3 deletions are novel. Furthermore, our finding of four whole exon duplications enlarges the mutation spectrum in the ATP7A gene. ATP7A alterations were found in 85% of cases. Of these alterations, two thirds were point mutations and the remaining one third consisted of large rearrangements. We found that 66.6% of point mutations resulted in impaired ATP7A transcript splicing, a phenomenon more frequent than expected. This finding enabled us to confirm the pathogenic role of ATP7A mutations, particularly in missense and splice site variants. |
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Authors:
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M-P Moizard; N Ronce; S Blesson; E Bieth; L Burglen; C Mignot; I Mortemousque; N Marmin; B Dessay; C Danesino; F Feillet; P Castelnau; A Toutain; C Moraine; M Raynaud |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2010-5-7 |
Journal Detail:
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Title: Clinical genetics Volume: - ISSN: 1399-0004 ISO Abbreviation: - Publication Date: 2010 May |
Date Detail:
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Created Date: 2011-1-6 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0253664 Medline TA: Clin Genet Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2010 John Wiley & Sons A/S. |
Affiliation:
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CHRU de Tours, Service de Génétique, Tours, F-37044, France INSERM U930, Tours, F-37044, France CHU Hôpital Purpan, Service de Génétique médicale, Toulouse, F-31059, France CHU Hôpital d'Enfants Armand-Trousseau, AP-HP, Service de Génétique et Embryologie médicales, Paris, F-75571, France CHU Hôpital d'Enfants Armand-Trousseau, AP-HP, Service de Neuropédiatrie, Paris, F-75012, France Genetica Medica, Università di Pavia, Fondazione IRCCS S. Matteo, Pavia, I-27100, Italie Centre de Référence des Maladies Héréditaires du Métabolisme, INSERM U954. Hôpital d'Enfants, Vandoeuvre les Nancy, F-54511, France CHRU de Tours, Service de Neuropédiatrie, Tours, F-37044 France; Université François Rabelais Tours, F-37044, France. |
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