Homozygous SMN1 deletions in unaffected family members and modification of the phenotype by SMN2

被引:128
作者
Prior, TW
Swoboda, KJ
Scott, HD
Hejmanowski, AQ
机构
[1] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA
[2] Univ Utah, Sch Med, Dept Neurol, Salt Lake City, UT USA
[3] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA
[4] Brown Med Sch, Mem Hosp Rhode Isl, Dept Med, Providence, RI USA
关键词
neuromuscular disorder; spinal muscular atrophy; SMN; discordant phenotype;
D O I
10.1002/ajmg.a.30251
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Spinal muscular atrophy is a common autosomal. recessive neuromuscular disorder caused by the homozygous loss of the SMN1 gene. The absence of the SMN1 gene has been shown to occur in all types of SMA, childhood and adult forms. In rare cases, asymptomatic family members have also been found with homozygous mutations in the SMN1 gene, suggesting a role for phenotypic modifiers. We describe three unrelated asymptomatic individuals, with family histories of SMA, who were shown to have the homozygous SMN1 deletion. Quantitative studies indicated that the three individuals all had increased SMN2 copy numbers. These cases not only support the role of SMN2 in modifying the phenotype, but our data also demonstrate that expression levels consistent with five copies of the SMN2 genes maybe enough to compensate for the absence of the SMN1 gene. Lastly, in cases similar to the ones described, the measurement of the SMN2 gene copy number may provide valuable prognostic information. (C) 2004 Wiley-Liss, Inc.
引用
收藏
页码:307 / 310
页数:4
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