Document Detail


Mutation spectrum in RAB3GAP1, RAB3GAP2, and RAB18 and genotype-phenotype correlations in warburg micro syndrome and Martsolf syndrome.
MedLine Citation:
PMID:  23420520     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Warburg Micro syndrome and Martsolf syndrome (MS) are heterogeneous autosomal-recessive developmental disorders characterized by brain, eye, and endocrine abnormalities. Causative biallelic germline mutations have been identified in RAB3GAP1, RAB3GAP2, or RAB18, each of which encode proteins involved in membrane trafficking. This report provides an up to date overview of all known disease variants identified in 29 previously published families and 52 new families. One-hundred and forty-four Micro and nine Martsolf families were investigated, identifying mutations in RAB3GAP1 in 41% of cases, mutations in RAB3GAP2 in 7% of cases, and mutations in RAB18 in 5% of cases. These are listed in Leiden Open source Variation Databases, which was created by us for all three genes. Genotype-phenotype correlations for these genes have now established that the clinical phenotypes in Micro syndrome and MS represent a phenotypic continuum related to the nature and severity of the mutations present in the disease genes, with more deleterious mutations causing Micro syndrome and milder mutations causing MS. RAB18 has not yet been linked to the RAB3 pathways, but mutations in all three genes cause an indistinguishable phenotype, making it likely that there is some overlap. There is considerable genetic heterogeneity for these disorders and further gene identification will help delineate these pathways.
Authors:
Mark T Handley; Deborah J Morris-Rosendahl; Stephen Brown; Fiona Macdonald; Carol Hardy; Danai Bem; Sarah M Carpanini; Guntram Borck; Loreto Martorell; Claudia Izzi; Francesca Faravelli; Patrizia Accorsi; Lorenzo Pinelli; Lina Basel-Vanagaite; Gabriela Peretz; Ghada M H Abdel-Salam; Maha S Zaki; Anna Jansen; David Mowat; Ian Glass; Helen Stewart; Grazia Mancini; Damien Lederer; Tony Roscioli; Fabienne Giuliano; Astrid S Plomp; Arndt Rolfs; John M Graham; Eva Seemanova; Pilar Poo; Angels García-Cazorla; Patrick Edery; Ian J Jackson; Eamonn R Maher; Irene A Aligianis
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human mutation     Volume:  34     ISSN:  1098-1004     ISO Abbreviation:  Hum. Mutat.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-12     Completed Date:  2013-09-30     Revised Date:  2014-10-28    
Medline Journal Info:
Nlm Unique ID:  9215429     Medline TA:  Hum Mutat     Country:  United States    
Other Details:
Languages:  eng     Pagination:  686-96     Citation Subset:  IM    
Copyright Information:
© 2013 Wiley Periodicals, Inc.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Cataract / genetics*,  pathology
Child
Child, Preschool
Genotype*
Humans
Hypogonadism / genetics*,  pathology
Infant
Intellectual Disability / genetics*,  pathology
Magnetic Resonance Imaging
Male
Molecular Sequence Data
Mutation, Missense*
Phenotype*
Sequence Homology, Amino Acid
rab GTP-Binding Proteins / chemistry,  genetics*
rab3 GTP-Binding Proteins / chemistry,  genetics*
Grant Support
ID/Acronym/Agency:
MC_PC_U127561112//Medical Research Council; MC_U127561112//Medical Research Council
Chemical
Reg. No./Substance:
0/RAB18 protein, human; 0/RAB3GAP2 protein, human; EC 3.6.1.-/rab GTP-Binding Proteins; EC 3.6.5.2/RAB3GAP1 protein, human; EC 3.6.5.2/rab3 GTP-Binding Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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