Abstract OBJECTIVE: To study the incidence of homozygous absence of SMN1 exons 7 and 8, SMN gene conversion frequency and SMN subtle mutations in children with spinal muscular atrophy (SMA). METHODS: The homozygous deletion was detected by PCR-RFLP in 106 Chinese children with SMA, gene conversion by RFLP and subtle mutations by sequencing. RESULTS: The rate of deletion of SMN1 exons 7 and/or 8 was 91.5%. Deletion of SMN1 exon 8 but existence of exon 7 was noted in one child with SMA. There were no significant differences in the gene conversion frequency among children with different types of SMA and who had homozygous deletion of SMN1 exon 7 but existence of exon 8. The gene conversion frequency was 8.3% in children with homozygous deletion of SMN1 exon 7. No subtle mutations were found around SMN1 exon 7. CONCLUSIONS: Deletion of SMN1 exons 7 and/or 8 is the main cause of SMA in Chinese children. There exists a SMN gene conversion phenomenon in SMA. Deletion of exon 8 might lead to SMA. The hot area of subtle mutations of this disease might not be around SMN1 exon 7. ［Chin J Contemp Pediatr, 2010, 12 (7):539-543］
［5］Mazzei R, Gambardella A, Conforti FL, Magariello A, Patitucci A, Gabriele AL, et al. Gene conversion events in adult-onset spinal muscular atrophy［J］. Acta Neurol Scand, 2004, 109(2):151-154.
［6］Wirth B. An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA) ［J］.Hum Mutat, 2000, 15(3):228-237.
3.0.CO;2-9 target="_blank">
［7］Derakhshandeh-Peykar P, Esmaili M, Ousati-Ashtiani Z, Rahmani M, Babrzadeh F, Farshidi S, et al. Molecular analysis of the SMN1 and NAIP genes in Iranian patients with spinal muscular atrophy［J］. Ann Acad Med Singapore, 2007, 36(11):937-941.
［8］Zapletalová E, Hedvicáková P, Kozák L, Vondrácek P, Gaillyová R, Maríková T, et al. Analysis of point mutations in the SMN1 gene in SMA patients bearing a single SMN1 copy［J］. Neuromuscul Disord, 2007, 7(6):476-481.
［9］Banyer JL, Goldwurm S, Cullen L, van der Griend B, Zournazi A, Smit DJ, et al. The spinal muscular atrophy gene region at 5q 13.1 has a paralogous chromosomal region at 6p21.3［J］ . Mamm Genome, 1998, 9(3):235-239.
［10］Kaindl AM, Guenther UP, Rudnik-Schoneborn S, Varon R, Zerres K, Schuelke M, et al. Spinal muscular atrophy with respiratory distress type 1 (SMARD1) ［J］. J Child Neurol, 2008, 23(2):199-204.
［11］Ogino S, Wilson RB. Spinal muscular atrophy: molecular genetics and diagnostics［J］. Expert Rev Mol Diagn, 2004, 4(1):15-29.
［12］Roy D, Yu K, Lieber MR. Mechanism of R-loop formation at immunoglobulin class switch sequences［J］. Mol Cell Biol, 2008, 28(1):50-60.
［13］Hahnen E, Schonling J, Rudnik-Schoneborn S. Hybrid survival motor neuron genes in patients with autosomal recessive spinal muscular atrophy: new insights into molecular mechanisms responsible for the disease［J］.Am J Hum Genet, 1996, 59(5):1057-1065.
［14］Kashima T, Rao N, Manley JL .An intronic element contributes to splicing repression in spinal muscular atrophy［J］. Proc Natl Acad Sci USA, 2007, 104(9):3426-3431.
