title: Somatic mosaicism for a heterozygous deletion of the survival motor neuron (SMN1) gene.
abstract: Infantile spinal muscular atrophy (SMA) is a common autosomal recessive disease with a high demand for carrier testing. The disease is caused by homozygous deletions of the survival motor neuron (SMN)1 gene on chromosome 5q13 in more than 90% of cases. Meanwhile, several reliable quantitative methods for carrier detection in the general population have been implemented with a risk of at least 5% for false negative results. Linkage analyses with chromosome 5 markers can be used for complementary information, but they are restricted to risk estimation of close relatives in affected families. Here, we present the first observation of a somatic mosaicism in an SMA carrier. Molecular genetic studies gave evidence that the SMN1 deletion of an SMA type I patient most probably arose from somatic mosaicism in the paternal grandmother. The patient's father and his two brothers were shown to be carriers of three different maternal haplotypes in 5q13. Final conclusions for genetic counselling were only possible after both linkage analysis and quantitative real-time PCR analysis of SMN1 copy numbers.
authors.affiliation: Institute of Human Genetics, University of Technology, Aachen, Germany. teggermann@ukaachen.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Eggermann
authors.forename: Klaus
authors.initials: K
authors.lastname: Zerres
authors.forename: Dirk
authors.initials: D
authors.lastname: Anhuf
authors.forename: Dieter
authors.initials: D
authors.lastname: Kotzot
authors.forename: Christine
authors.initials: C
authors.lastname: Fauth
authors.forename: Sabine
authors.initials: S
authors.lastname: Rudnik-Schöneborn
mesh_terms: D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006580:Genetic Carrier Screening / Q000379:methods*; D005817:Genetic Counseling; D006579:Heterozygote; D006801:Humans; D008297:Male; D009030:Mosaicism; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D016601:RNA-Binding Proteins / Q000235:genetics*; D055532:SMN Complex Proteins; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics*; D055533:Survival of Motor Neuron 1 Protein
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein