目的:Bardet-Biedl综合征(BBS)是一种多系统遗传性疾病,这在高加索人群中并不普遍,具有高度可变的表型和巨大的遗传异质性。BBS属于一组称为纤毛病的疾病,由纤毛的结构和/或功能缺陷引起的。由于该综合征的诊断复杂性,这项研究的目的是分析我们的整组患者,以创建一种算法来促进BBS的常规分子诊断.我们还计算了我们队列中的几个流行病学参数。
方法:我们分析了来自整个西班牙地理的89个家庭的116例BBS患者。所有先证者均符合为BBS建立的诊断标准。为此,我们使用:基因分型微阵列,直接测序和纯合子作图(近亲家族)。
结果:通过不同的方法,可以诊断47%的家庭(21%通过基因分型微阵列,18%通过对主要的BBS基因直接测序,和8%的纯合子作图)。关于流行病学数据,在西班牙,BBS的患病率值为1:407,000,性别比例为1.4:1(男性:女性)。
结论:提出的算法,在结合纯合子图谱分析优势BBS基因的基础上,使我们能够确认相当比例的临床可疑BBS家庭的分子诊断。该诊断算法将有助于提高BBS中分子分析的效率。
OBJECTIVE: Bardet-Biedl syndrome (BBS) is a multisystemic genetic disorder, which is not widespread among the Caucasian population, characterized by a highly variable phenotype and great genetic heterogeneity. BBS belongs to a group of diseases called ciliopathies, caused by defects in the structure and/or function of cilia. Due to the diagnostic complexity of the syndrome, the objective of this study was to analyse our whole group of patients in order to create an algorithm to facilitate the routine molecular diagnosis of BBS. We also calculated several epidemiological parameters in our cohort.
METHODS: We analysed 116 BBS patients belonging to 89 families from the whole Spanish geography. All probands fulfilled diagnosis criteria established for BBS. For this, we used: genotyping microarray, direct sequencing and homozygosis mapping (in consanguineous families).
RESULTS: By means of the different approaches, it was possible to diagnose 47% of families (21% by genotyping microarray, 18% by direct sequencing of predominant BBS genes, and 8% by homozygosis mapping). With regard to epidemiological data, a prevalence value of 1:407,000 was obtained for BBS in Spain, and a sex ratio of 1.4:1 (men:women).
CONCLUSIONS: The proposed algorithm, based on the analysis of predominant BBS genes combined with homozygosis mapping, allowed us to confirm the molecular diagnosis in a significant percentage of families with clinically suspected BBS. This diagnostic algorithm will be useful for the improvement of the efficiency of molecular analysis in BBS.