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Hum Genet. 2003 Feb;112(2):209-16. Epub 2002 Nov 16.

Fine structure mapping of CIAS1: identification of an ancestral haplotype and a common FCAS mutation, L353P.

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1
Division of Rheumatology, Allergy, and Immunology, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093-0635, USA. hahoffman@ucsd.edu

Abstract

Familial cold autoinflammatory syndrome (FCAS) is an autosomal dominant inflammatory disease with a high degree of penetrance that is characterized by episodes of rash, arthralgia, fever, conjunctivitis, and leukocytosis after generalized exposure to cold. FCAS was previously mapped to a 10-cM region on chromosome 1q44, and subsequently the gene ( CIAS1) responsible for FCAS was identified. In this paper, we describe the physical and genetic mapping of the FCAS locus, and we report a large ancestral haplotype and a new disease-causing mutation. A BAC contig of approximately 3 Mb was developed and subsequently used for high throughput sequencing. We identified a critical region of 4 cM using rare crossover events in four large North American FCAS families. An unusually large shared haplotype (40 cM) was identified in three of the four families. We found a single heterozygous missense mutation (T1058C=L353P) in exon 3 of CIAS1 in all four families that is responsible for the large majority of FCAS cases described in the literature. We also report a comprehensive list of intragenic single nucleotide polymorphisms. The data provided here will assist others researching the 1q44 region and will aid clinicians in the diagnosis of FCAS.

PMID:
12522564
DOI:
10.1007/s00439-002-0860-x
[Indexed for MEDLINE]
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