| The first missense alteration in the MCPH1 gene causes autosomal recessive microcephaly with an extremely mild cellular and clinical phenotype. | |
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MedLine Citation:
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PMID: 16211557 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Autosomal recessive primary microcephaly (MCPH) is a rare neurodevelopmental disorder characterized by mental retardation and congenital microcephaly with a head circumference at least 4 SD below age and sex means, in the absence of other significant malformations or neurological deficits. Truncating alterations in the MCPH1 gene have previously been shown to exhibit a distinct cellular phenotype, with a high proportion of prophase-like cells (>10%) due to premature chromosome condensation in early G2- and delayed decondensation in early G1-phase of the cell cycle. We report here the first patient with a homozygous substitution of a highly conserved threonine residue by an arginine (c.80C>G, Thr27Arg) localized in the N-terminal BRCT domain of MCPH1. The cellular and clinical phenotype of this patient is much less pronounced than that of previously described patients with truncating alterations in the MCPH1 gene. Firstly, the fraction of prophase-like cells accounts for just 3-4% of the cell population. Secondly, clinically, he has only a very mild mental retardation with predominantly delayed motor skills but normal verbal IQ attainment. Additionally, head circumference was less severely affected, being -2.4 SD at birth and -3 SD at the age of six years. This justifies reconsideration and widening of the clinical phenotype definition of MCPH1. |
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Authors:
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Marc Trimborn; Reyk Richter; Nadine Sternberg; Ioannis Gavvovidis; Detlev Schindler; Andrew P Jackson; Eva-Christina Prott; Karl Sperling; Gabriele Gillessen-Kaesbach; Heidemarie Neitzel |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Human mutation Volume: 26 ISSN: 1098-1004 ISO Abbreviation: Hum. Mutat. Publication Date: 2005 Nov |
Date Detail:
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Created Date: 2005-10-18 Completed Date: 2006-06-13 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9215429 Medline TA: Hum Mutat Country: United States |
Other Details:
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Languages: eng Pagination: 496 Citation Subset: IM |
Copyright Information:
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Copyright 2005 Wiley-Liss, Inc. |
Affiliation:
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Institut für Humangenetik, Charité - Universitätsmedizin Berlin, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Cells, Cultured Child Chromosomes / ultrastructure DNA Mutational Analysis European Continental Ancestry Group / ethnology Humans Male Mental Retardation / genetics Microcephaly / diagnosis*, genetics*, pathology Molecular Sequence Data Mutation, Missense* Nerve Tissue Proteins / genetics* Phenotype Sequence Alignment T-Lymphocytes / pathology |
| Chemical | |
Reg. No./Substance:
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0/MCPH1 protein, human; 0/Nerve Tissue Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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