| A homozygous RAB3GAP2 mutation causes Warburg Micro syndrome. | |
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MedLine Citation:
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PMID: 20967465 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Warburg Micro syndrome and Martsolf syndrome are clinically overlapping autosomal recessive conditions characterized by congenital cataracts, microphthalmia, postnatal microcephaly, and developmental delay. The neurodevelopmental and ophthalmological phenotype is more severe in Warburg Micro syndrome in which cerebral malformations and severe motor and mental retardation are common. While biallelic loss-of-function mutations in RAB3GAP1 are present in the majority of patients with Warburg Micro syndrome; a hypomorphic homozygous splicing mutation of RAB3GAP2 has been reported in a single family with Martsolf syndrome. Here, we report a novel homozygous RAB3GAP2 small in-frame deletion, c.499_507delTTCTACACT (p.Phe167_Thr169del) that causes Warburg Micro syndrome in a girl from a consanguineous Turkish family presenting with congenital cataracts, microphthalmia, absent visually evoked potentials, microcephaly, polymicrogyria, hypoplasia of the corpus callosum, and severe developmental delay. No RAB3GAP2 mutations were detected in ten additional unrelated patients with RAB3GAP1-negative Warburg Micro syndrome, consistent with further genetic heterogeneity. In conclusion, we provide evidence that RAB3GAP2 mutations are not specific to Martsolf syndrome. Rather, our findings suggest that loss-of-function mutations of RAB3GAP1 as well as functionally severe RAB3GAP2 mutations cause Warburg Micro syndrome while hypomorphic RAB3GAP2 mutations can result in the milder Martsolf phenotype. Thus, a phenotypic severity gradient may exist in the RAB3GAP-associated disease continuum (the "Warburg-Martsolf syndrome") which is presumably determined by the mutant gene and the nature of the mutation. |
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Authors:
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Guntram Borck; Heidrun Wunram; Angela Steiert; Alexander E Volk; Friederike Körber; Sigrid Roters; Peter Herkenrath; Bernd Wollnik; Deborah J Morris-Rosendahl; Christian Kubisch |
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Publication Detail:
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Type: Case Reports; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-22 |
Journal Detail:
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Title: Human genetics Volume: 129 ISSN: 1432-1203 ISO Abbreviation: Hum. Genet. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-03 Completed Date: 2011-02-02 Revised Date: 2011-03-29 |
Medline Journal Info:
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Nlm Unique ID: 7613873 Medline TA: Hum Genet Country: Germany |
Other Details:
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Languages: eng Pagination: 45-50 Citation Subset: IM |
Affiliation:
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Institute of Human Genetics, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany. guntram.borck@uk-koeln.de |
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| MeSH Terms | |
Descriptor/Qualifier:
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Abnormalities, Multiple
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genetics Base Sequence Cataract / congenital, genetics Consanguinity Cornea / abnormalities Corpus Callosum / abnormalities Exons / genetics Female Genetic Predisposition to Disease Homozygote* Humans Hypogonadism / genetics Infant Mental Retardation / genetics Microcephaly / genetics Molecular Sequence Data Optic Atrophy / genetics RNA Splicing / genetics Sequence Deletion* rab3 GTP-Binding Proteins / genetics* |
| Chemical | |
Reg. No./Substance:
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0/RAB3GAP2 protein, human; EC 3.6.5.2/rab3 GTP-Binding Proteins |
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