Document Detail


Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alström syndrome.
MedLine Citation:
PMID:  11941370     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Alström syndrome (OMIM 203800) is an autosomal recessive disease, characterized by cone-rod retinal dystrophy, cardiomyopathy and type 2 diabetes mellitus, that has been mapped to chromosome 2p13 (refs 1-5). We have studied an individual with Alström syndrome carrying a familial balanced reciprocal chromosome translocation (46, XY,t(2;11)(p13;q21)mat) involving the previously implicated critical region. We postulated that this individual was a compound heterozygote, carrying one copy of a gene disrupted by the translocation and the other copy disrupted by an intragenic mutation. We mapped the 2p13 breakpoint on the maternal allele to a genomic fragment of 1.7 kb which contains exon 4 and the start of exon 5 of a newly discovered gene (ALMS1); we detected a frameshift mutation in the paternal copy of the gene. The 12.9-kb transcript of ALMS1 encodes a protein of 4,169 amino acids whose function is unknown. The protein contains a large tandem-repeat domain comprising 34 imperfect repetitions of 47 amino acids. We have detected six different mutations (two nonsense and four frameshift mutations causing premature stop codons) in seven families, confirming that ALMS1 is the gene underlying Alström syndrome. We believe that ALMS1 is the first human disease gene characterized by autosomal recessive inheritance to be identified as a result of a balanced reciprocal translocation.
Authors:
Tom Hearn; Glenn L Renforth; Cosma Spalluto; Neil A Hanley; Karen Piper; Sarah Brickwood; Chris White; Vincent Connolly; James F N Taylor; Isabelle Russell-Eggitt; Dominque Bonneau; Mark Walker; David I Wilson
Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't     Date:  2002-04-08
Journal Detail:
Title:  Nature genetics     Volume:  31     ISSN:  1061-4036     ISO Abbreviation:  Nat. Genet.     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-05-01     Completed Date:  2002-05-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  79-83     Citation Subset:  IM    
Affiliation:
Division of Human Genetics, Southampton University, The Duthie Building, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/AJ417593
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Cardiomyopathies / genetics*
Chromosomes, Human, Pair 11 / genetics
Chromosomes, Human, Pair 2 / genetics
Diabetes Mellitus, Type 2 / genetics*
Female
Genes, Recessive
Humans
In Situ Hybridization, Fluorescence
Male
Molecular Sequence Data
Mutation*
Retinal Degeneration / genetics*
Sequence Homology, Amino Acid
Syndrome
Tandem Repeat Sequences*
Translocation, Genetic

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


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