Open AccessThe frequency of SMN gene variants lacking exon 7 and 8 is highly population dependent
Author(s) -
Raymon Vijzelaar,
Reinier Snetselaar,
M. J. A. M. Clausen,
Amanda G. Mason,
Marrit Rinsma,
Marinka Zegers,
Naomi N. Molleman,
Renske Boschloo,
Rizkat Yilmaz,
Romy Kuilboer,
Sylvia I. Lens,
Syamiroh Sulchan,
Jan P. Schouten
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0220211
Subject(s) - smn1 , spinal muscular atrophy , multiplex ligation dependent probe amplification , exon , sma* , biology , genetics , population , gene , copy number variation , microbiology and biotechnology , genome , medicine , mathematics , environmental health , combinatorics
Spinal Muscular Atrophy (SMA) is a disorder characterized by the degeneration of motor neurons in the spinal cord, leading to muscular atrophy. In the majority of cases, SMA is caused by the homozygous absence of the SMN1 gene. The disease severity of SMA is strongly influenced by the copy number of the closely related SMN2 gene. In addition, an SMN variant lacking exons 7 and 8 has been reported in 8% and 23% of healthy Swedish and Spanish individuals respectively. We tested 1255 samples from the 1000 Genomes Project using a new version of the multiplex ligation-dependent probe amplification (MLPA) P021 probemix that covers each SMN exon. The SMN variant lacking exons 7 and 8 was present in up to 20% of individuals in several Caucasian populations, while being almost completely absent in various Asian and African populations. This SMN1/2Δ7–8 variant appears to be derived from an ancient deletion event as the deletion size is identical in 99% of samples tested. The average total copy number of SMN1 , SMN2 and the SMN1/2Δ7–8 variant combined was remarkably comparable in all populations tested, ranging from 3.64 in Asian to 3.75 in African samples.