Ogino Shuji, Leonard Debra G B, Rennert Hanna, Ewens Warren J, Wilson Robert B
Molecular Pathology Laboratory, Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, USA.
Am J Med Genet. 2002 Jul 15;110(4):301-7. doi: 10.1002/ajmg.10425.
As evidenced by the complete absence of a functionally critical sequence in exon 7, approximately 94% of individuals with clinically typical spinal muscular atrophy (SMA) lack both copies of the SMN1 gene at 5q13. Hence most carriers have only one copy of SMN1. Combining linkage and dosage analyses for SMN1, we observed unaffected individuals who have two copies of SMN1 on one chromosome 5 and zero copies of SMN1 on the other chromosome 5. By dosage analysis alone, such individuals, as well as carriers of non-deletion disease alleles, are indistinguishable from non-carrier individuals. We report that approximately 7% of unaffected individuals without a family history of SMA have three or four copies of SMN1, implying a higher frequency of chromosomes with two copies of SMN1 than previously reported. We present updated calculations for disease and non-disease allele frequencies and we describe how these frequencies can be used for genetic risk assessment in carrier testing for SMA.
正如外显子7中完全不存在功能关键序列所证明的那样，约94%临床典型脊髓性肌萎缩症（SMA）患者在5q13处缺失SMN1基因的两个拷贝。因此，大多数携带者只有一个SMN1拷贝。通过对SMN1进行连锁和剂量分析，我们观察到未受影响的个体，其中一条5号染色体上有两个SMN1拷贝，而另一条5号染色体上没有SMN1拷贝。仅通过剂量分析，这些个体以及非缺失疾病等位基因的携带者与非携带者个体无法区分。我们报告称，约7%无SMA家族史的未受影响个体有三个或四个SMN1拷贝，这意味着含有两个SMN1拷贝的染色体频率高于先前报道。我们给出了疾病和非疾病等位基因频率的最新计算结果，并描述了这些频率如何用于SMA携带者检测中的遗传风险评估。
