Evidence of autosomal dominant mutations in childhood-onset proximal spinal muscular atrophy.
Evidence of autosomal dominant mutations in childhood-onset proximal spinal muscular atrophy.
复制标题
儿童期发病的近端脊髓性肌萎缩症常染色体显性突变的证据。
DOI：
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发表时间：
1994
影响因子：
9.8
通讯作者：
Klaus Zerres
中科院分区：
文献类型：
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作者：
S. Rudnik;Brunhilde Wirth;Klaus Zerres
近端型脊髓性肌萎缩症（SMA）的常染色体隐性和显性遗传已被充分证实。几项遗传学研究发现，SMA的隐性遗传假设存在显着偏差，一代人中就有受影响的儿童。新的常染色体显性突变的存在被认为是最合适的突变，这得到了本研究的三个观察结果的支持：（1）333个家系的分离比表明，轻度SMA与常染色体隐性遗传有明显的偏离（P = 0.09 +/- .06，10-36个月时发作; P = 0.13 +/- .07，> 36个月时发作; P = 0.09 +/- .07，SMA IIIa和SMA IIIb）。(2)三个家庭的受影响的主题在两代人的报告，在这些疾病可能已经开始作为一个常染色体显性突变。(3)染色体5 q标记的连锁研究表明，在5（5.4%）的93个提供信息的家庭中，患者与至少一个健康同胞共享相同的单倍型。其他机制，如表型复制，假显性，或第二个常染色体隐性基因位点的存在，不能排除在单个家庭。然而，自发突变的假设是对所有三种观察结果的适当解释。遗传咨询的估计风险数字。
Autosomal recessive and dominant inheritance of proximal spinal muscular atrophy (SMA) are well documented. Several genetic studies found a significant deviation from the assumption of recessive inheritance in SMA, with affected children in one generation. The existence of new autosomal dominant mutations has been assumed as the most suitable explantation, which is supported by three observations of this study: (1) The segregation ratio calculated in 333 families showed a significant deviation from autosomal recessive inheritance in the milder forms of SMA (P = .09 +/- .06 for onset at 10-36 mo and .13 +/- .07 for onset at > 36 mo; and P = .09 +/- .07 for SMA IIIa and .12 +/- .07 for SMA IIIb). (2) Three families with affected subjects in two generations are reported, in whom the disease could have started as an autosomal dominant mutation. (3) Linkage studies with chromosome 5q markers showed that in 5 (5.4%) of 93 informative families the patient shared identical haplotypes with at least one healthy sib. Other mechanisms, such as the existence of phenocopies, pseudodominance, or a second autosomal recessive gene locus, cannot be excluded in single families. The postulation of spontaneous mutations, however, is a suitable explanation for all three observations. Estimated risk figures for genetic counseling are given.