Improving detection and genetic counseling in carriers of spinal muscular atrophy with two copies of the SMN1 gene. (16th July 2013)

• Record Type: Journal Article
• Authors: Alías, L.; Barceló, M.J.; Bernal, S.; Martínez‐Hernández, R.; Also‐Rallo, E.; Vázquez, C.; Santana, A.; Millán, J.M.; Baiget, M.; Tizzano, E.F.
• Is Part Of: Clinical genetics. Volume 85:Number 5(2014:May)
• Page Start: 470
• Page End: 475
• Publication Date: 2013-07-16
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12222
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main" id="cge12222-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p id="cge12222-para-0001">Spinal muscular atrophy (SMA) is an autosomal recessive disease caused by mutations in the survival motor neuron1 gene (<italic>SMN1</italic>). Global carrier frequency is around 1 in 50 and carrier detection is crucial to define couples at risk to have SMA offspring. Most SMA carriers have one <italic>SMN1</italic> copy and are currently detected using quantitative methods. A few, however, have two <italic>SMN1</italic> genes in <italic>cis</italic> (2/0 carriers), complicating carrier diagnosis in SMA. We analyzed our experience in detecting 2/0 carriers from a cohort of 1562 individuals, including SMA parents, SMA relatives, and unrelated individuals of the general population. Interestingly, in three couples who had an SMA child, both the parents had two <italic>SMN1</italic> copies. Families of this type have not been previously reported. Our results emphasize the importance of performing a detailed carrier study in SMA parents with two <italic>SMN1</italic> copies. Expanding the analysis to other key family members might confirm potential 2/0 carriers. Finally, when a partner of a known carrier presents two <italic>SMN1</italic> copies, the study of both parents will provide a more accurate diagnosis, thus optimizing genetic counseling.</p> </abstract>