Hybrids monosomal for human chromosome 5 reveal the presence of a spinal muscular atrophy (SMA) carrier with two SMN1 copies on one chromosome

We have analyzed the survival motor neuron gene (SMN1) dosage in 100 parents of children with homozygous SMN1 deletions. Of these parents, 96 (96%) demonstrated the expected one-copy SMN1 carrier genotype. However, four parents (4%) were observed to have a normal two-copy SMN1 dosage. The presence o...

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Bibliographic Details
Published in:Human genetics 2001-02, Vol.108 (2), p.109-115
Main Authors: MAILMAN, Matthew D, HEMINGWAY, Tamara, SCHAFER, Robert W, ABUELO, Dianne N, REICH, Elsa W, THEIL, Karl S, BURGHES, Arthur H. M, DE LA CHAPELLE, Albert, PRIOR, Thomas W, DARSEY, Rebecca L, GLASURE, Carol E, YING HUANG, CHADWICK, Robert B, HEINZ, John W, PAPP, Audrey C, SNYDER, Pamela J, SEDRA, Mary S
Format: Article
Language:English
Subjects:
Autoradiography
Base Sequence
Biological and medical sciences
Chromosome Mapping
Chromosomes, Human, Pair 5
Cyclic AMP Response Element-Binding Protein
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
DNA Primers
Genetic Carrier Screening
Haplotypes
Humans
In Situ Hybridization, Fluorescence
Medical sciences
Muscular Atrophy, Spinal - genetics
Mutation
Nerve Tissue Proteins - genetics
Neurology
RNA-Binding Proteins
SMN Complex Proteins
Survival of Motor Neuron 1 Protein
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Summary:We have analyzed the survival motor neuron gene (SMN1) dosage in 100 parents of children with homozygous SMN1 deletions. Of these parents, 96 (96%) demonstrated the expected one-copy SMN1 carrier genotype. However, four parents (4%) were observed to have a normal two-copy SMN1 dosage. The presence of two intact SMN1 genes in the parent of an affected child indicates either the occurrence of a de novo mutation event or a situation in which one chromosome has two copies of SMN1, whereas the other is null. We have separated individual chromosomes from two of these parents with two-copy SMN1 dosage by somatic cell hybridization and have employed a modified quantitative dosage assay to provide direct evidence that one parent is a two-copy/ zero-copy SMN1 carrier, whereas the other parent had an affected child as the result of a de novo mutation. These findings are important for assessing the recurrence risk of parents of children with spinal muscular atrophy and for providing accurate family counseling.
ISSN:0340-6717
1432-1203
DOI:10.1007/s004390000446