National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Genet Med. 2010 Oct;12(10):623-7. doi: 10.1097/GIM.0b013e3181f07572.
Bardet-Biedl syndrome is a pleiotropic multiple anomaly syndrome inherited in an autosomal recessive pattern. It is now known that this disorder has locus heterogeneity, with causative mutations identified in as many as 14 genes. The aim of this study was to derive locus-specific recurrence risk estimates for family members of a proband affected with Bardet-Biedl syndrome.
Mutation data from 187 probands affected with Bardet-Biedl syndrome were used. The authors counted the relative proportion of families with mutations at each of 10 loci and estimated locus-specific carrier rates for mutations using Hardy-Weinberg principles and an aggregate population frequency of 1/100,000 for the phenotype. Locus-specific recurrence risks were calculated for relatives of an affected proband.
Locus-specific carrier frequencies range from 1/250 to 1/2200, and the risks for an offspring of the sibling of an affected individual range from 1/1,500 to 1/13,000. The estimate of this risk derived under a locus homogeneity model is 1/960.
Variation of recurrence risks of this magnitude may have implications for genetic counseling of families with affected individuals, in particular about prenatal testing and other reproductive options. Similar analyses to determine locus-specific carrier frequencies for other phenotypes with significant locus heterogeneity may yield similarly relevant results.
Bardet-Biedl 综合征是一种多系统常染色体隐性遗传病，具有明显的遗传异质性，目前已发现至少 14 个基因与该病相关。本研究旨在计算 Bardet-Biedl 综合征先证者家系成员的发病风险。
使用 187 例 Bardet-Biedl 综合征先证者的基因突变数据，通过计算 10 个基因座突变的相对比例，应用 Hardy-Weinberg 原理和人群中该表型的频率（1/100000）计算各基因座突变的携带者频率，计算先证者同胞子女的发病风险。
各基因座突变的携带者频率为 1/2501/2200，先证者同胞子女的发病风险为 1/15001/13000，按基因座一致模型计算的发病风险为 1/960。
发病风险的这种程度的差异可能会影响到先证者家系的遗传咨询，特别是产前诊断和其他生殖选择。对其他具有显著基因座异质性的疾病进行类似的分析，可能会得到同样有意义的结果。
