Genomic rearrangements in childhood spinal muscular atrophy: linkage disequilibrium with a null allele

• Published in: Journal of medical genetics Vol. 32; no. 2; pp. 93 - 96
• Main Authors: Daniels, R J, Campbell, L, Rodrigues, N R, Francis, M J, Morrison, K E, McLean, M, MacKenzie, A, Ignatius, J, Dubowitz, V, Davies, K E
• Format: Journal Article Conference Proceeding
• Language: English
• Published: London BMJ Publishing Group Ltd 01.02.1995; BMJ; BMJ Publishing Group LTD
• Subjects: Alleles; Biological and medical sciences; Cerebrospinal fluid. Meninges. Spinal cord; Child; Chromosomes, Human, Pair 5 - genetics; DNA Probes; DNA, Satellite - genetics; Female; Finland; Gene Deletion; Gene Rearrangement - genetics; Genes, Recessive - genetics; Humans; Linkage Disequilibrium - genetics; Male; Medical sciences; Muscular Atrophy, Spinal - genetics; Nervous system (semeiology, syndromes); Neurology; Pedigree; Polymorphism, Genetic; Finland; Human; Neuromuscular diseases; Nervous system diseases; Linkage; Silent allele; Spinal amyotrophy; Linkage equilibrium; Central nervous system disease; Genetics; Degenerative disease; Molecular biology; Spinal cord disease; Child
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.32.2.93

Autosomal recessive childhood onset spinal muscular atrophy has been mapped to chromosome 5q13. We report the analysis of a polymorphic microsatellite which shows linkage disequilibrium with the disease. The linkage disequilibrium is observed with a null allele which is seen as the non-inheritance of alleles from one or both parents. The inheritance of a null allele was observed in 26 out of 36 (72%) informative childhood onset spinal muscular atrophy (SMA) families tested, of all types of severity and from a variety of ethnic backgrounds. In seven families segregating for the severe Werdnig-Hoffmann or SMA type I, no alleles were inherited from either parent using this microsatellite. This null allele may represent a deletion which is either closely associated with, or causes, the disease.