Holt-Oram syndrome is a genetically heterogeneous disease with one locus mapping to human chromosome 12q

• Published in: Nature genetics Vol. 6; no. 4; pp. 401 - 404
• Main Authors: Terrett, Jonathan A, Newbury-Ecob, Ruth, Cross, Gareth S, Fenton, Iain, Raeburn, J. Alexander, Young, Ian D, Brook, J. David
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.04.1994
• Subjects: Abnormalities, Multiple - classification; Abnormalities, Multiple - genetics; Arm - abnormalities; Biological and medical sciences; chromosome 12; Chromosome Mapping; Chromosomes, Human, Pair 12; Crossing Over, Genetic; Diseases of the osteoarticular system; DNA, Satellite - genetics; Female; Genes, Dominant; Genetic Markers; Hand Deformities, Congenital - classification; Hand Deformities, Congenital - genetics; heart; Heart Defects, Congenital - classification; Heart Defects, Congenital - genetics; Holt-Oram syndrome; Humans; limb; linkage analysis; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; man; Medical sciences; Pedigree; Syndrome; Genetic mapping; Human; Heterogeneity; Linkage; Heart disease; C12-Chromosome; Diseases of the osteoarticular system; Cardiovascular disease; Dysostosis; Holt Oram syndrome; Upper limb; Genetic disease
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng0494-401

Holt-Oram syndrome (HOS) is an autosomal dominant condition affecting the heart and upper limbs. We have sought to identify the location of this gene using microsatellite DNA markers in a linkage study. Of seven families analysed, five show linkage between HOS and markers on chromosome 12q. But the two remaining families, phenotypically indistinguishable from the others, do not show this linkage. Analysis with the computer program HOMOG indicates that HOS is a heterogeneous disease. Our analysis places one HOS locus in a 21 cM interval in the distal region of chromosome 12q. The localization of a gene for HOS, reported here, represents an important step towards a better understanding of limb and cardiac development.