サイトウ　カヨコ   Saito Kayoko   齋藤　加代子    所属   医学部 医学科（東京女子医科大学病院）    職種   特任教授
論文種別	原著
言語種別	英語
査読の有無	査読なし
表題	Spinal muscular atrophy carriers with two SMN1 copies.
掲載誌名	正式名：Brain & development 略　 称：Brain Dev ISSNコード：18727131/03877604
掲載区分	国外
巻・号・頁	39(10),pp.851-860
著者・共著者	Ar Rochmah Mawaddah, Awano Hiroyuki, Awaya Tomonari, Harahap Nur Imma Fatimah, Morisada Naoya, Bouike Yoshihiro, Saito Toshio, Kubo Yuji, Saito Kayoko, Lai Poh San, Morioka Ichiro, Iijima Kazumoto, Nishio Hisahide, Shinohara Masakazu
発行年月	2017/11
概要	BACKGROUND:Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder. Over 95% of SMA patients have homozygous deletions of the SMA-causative gene, SMN1. Thus, SMA carriers are usually diagnosed based on SMN1 copy number, with one copy indicating SMA carrier status. However, two SMN1 copies do not always exclude carrier status. In this study, we identified SMA carriers with two SMN1 copies.SUBJECTS AND METHODS:From 33 families, 65 parents of genetically confirmed SMA patients were tested to determine SMA carrier status. Molecular genetic analyses, including multiplex ligation-dependent probe amplification (MLPA) assay, were performed using blood samples from family members.RESULTS:Of the 65 parents, three parents from three families had two SMN1 copies. Accordingly, the frequency of carriers with two SMN1 copies was 4.6%. Two of these families were further studied. Patient 1 was homozygous for SMN1 deletion. Patient 1's mother had two SMN1 copies on one chromosome, with deletion of SMN1 on the other chromosome ([2+0] genotype). Patient 1 inherited SMN1-deleted chromosomes from both parents. Patient 2 was compound heterozygous for two SMN1 mutations: whole-gene deletion and intragenic missense mutation, c.826T>C (p.Tyr276His). Patient 2's father had two SMN1 copies with the same intragenic mutation in one copy ([1+1d] genotype, d intragenic mutation). Patient 2 inherited the chromosome with an SMN1 mutation from the father and SMN1-deleted chromosome from the mother.CONCLUSION:SMA carriers with two SMN1 copies may be rare, but its possibility should be taken into consideration in carrier testing and counseling for SMA families or population-based carrier screening.
DOI	10.1016/j.braindev.2017.06.002
PMID	28676237