| Distinct effects of allelic NFIX mutations on nonsense-mediated mRNA decay engender either a Sotos-like or a Marshall-Smith syndrome. | |
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MedLine Citation:
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PMID: 20673863 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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By using a combination of array comparative genomic hybridization and a candidate gene approach, we identified nuclear factor I/X (NFIX) deletions or nonsense mutation in three sporadic cases of a Sotos-like overgrowth syndrome with advanced bone age, macrocephaly, developmental delay, scoliosis, and unusual facies. Unlike the aforementioned human syndrome, Nfix-deficient mice are unable to gain weight and die in the first 3 postnatal weeks, while they also present with a spinal deformation and decreased bone mineralization. These features prompted us to consider NFIX as a candidate gene for Marshall-Smith syndrome (MSS), a severe malformation syndrome characterized by failure to thrive, respiratory insufficiency, accelerated osseous maturation, kyphoscoliosis, osteopenia, and unusual facies. Distinct frameshift and splice NFIX mutations that escaped nonsense-mediated mRNA decay (NMD) were identified in nine MSS subjects. NFIX belongs to the Nuclear factor one (NFI) family of transcription factors, but its specific function is presently unknown. We demonstrate that NFIX is normally expressed prenatally during human brain development and skeletogenesis. These findings demonstrate that allelic NFIX mutations trigger distinct phenotypes, depending specifically on their impact on NMD. |
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Authors:
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Valérie Malan; Diana Rajan; Sophie Thomas; Adam C Shaw; Hélène Louis Dit Picard; Valérie Layet; Marianne Till; Arie van Haeringen; Geert Mortier; Sheela Nampoothiri; Silvija Puseljić; Laurence Legeai-Mallet; Nigel P Carter; Michel Vekemans; Arnold Munnich; Raoul C Hennekam; Laurence Colleaux; Valérie Cormier-Daire |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-30 |
Journal Detail:
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Title: American journal of human genetics Volume: 87 ISSN: 1537-6605 ISO Abbreviation: Am. J. Hum. Genet. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-10 Completed Date: 2010-09-01 Revised Date: 2011-07-25 |
Medline Journal Info:
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Nlm Unique ID: 0370475 Medline TA: Am J Hum Genet Country: United States |
Other Details:
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Languages: eng Pagination: 189-98 Citation Subset: IM |
Affiliation:
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Département de Génétique, Université Paris Descartes, Hôpital Necker-Enfants Malades, Paris 75015, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Abnormalities, Multiple
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genetics* Adolescent Adult Alleles* Base Sequence Child Chromosomes, Human, Pair 19 / genetics Codon, Nonsense / genetics* Comparative Genomic Hybridization DNA Mutational Analysis Female Gene Expression Regulation Genetic Testing Humans In Situ Hybridization Male Molecular Sequence Data Mutation / genetics* NFI Transcription Factors / genetics*, metabolism RNA Stability / genetics* RNA, Messenger / genetics Reverse Transcriptase Polymerase Chain Reaction Syndrome |
| Chemical | |
Reg. No./Substance:
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0/Codon, Nonsense; 0/NFI Transcription Factors; 0/RNA, Messenger |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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