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Abstract：
BACKGROUND: Bardet-Biedl syndrome (BBS) is a type of non-motile ciliopathy. To date, 26 genes have been reported to be associated with BBS. However, BBS is genetically heterogeneous, with significant clinical overlap with other ciliopathies, which complicates diagnosis. Disability and mortality rates are high in BBS patients; therefore, it is urgent to improve our understanding of BBS. Thus, our study aimed to describe the genotypic and phenotypic spectra of BBS in China and to elucidate genotype-phenotype correlations.
METHODS: Twenty Chinese patients diagnosed with BBS were enrolled in this study. We compared the phenotypes of Chinese BBS patients in this study with those from other countries to analyze the phenotypic differences across patients worldwide. In addition, genotype-phenotype correlations were described for our cohort. We also summarized all previously reported cases of BBS in Chinese patients (71 patients) and identified common and specific genetic variants in the Chinese population.
RESULTS: Twenty-eight variants, of which 10 are novel, in 5 different BBS-associated genes were identified in 20 Chinese BBS patients. By comparing the phenotypes of BBSome-coding genes (BBS2,7,9) with those of chaperonin-coding genes (BBS10,12), we found that patients with mutations in BBS10 and 12 had an earlier age of onset (1.10 Vs. 2.20, p < 0.01) and diagnosis (4.64 Vs. 13.17, p < 0.01), whereas patients with mutations in BBS2, 7, and 9 had a higher body mass index (28.35 Vs. 24.21, p < 0.05) and more vision problems (p < 0.05). Furthermore, in 91 Chinese BBS patients, mutations were predominant in BBS2 (28.89%) and BBS7 (15.56%), and the most frequent variants were in BBS2: c.534 + 1G > T (10/182 alleles) and BBS7: c.1002delT (7/182 alleles), marking a difference from the genotypic spectra of BBS reported abroad.
CONCLUSIONS: We recruited 20 Chinese patients with BBS for genetic and phenotypic analyses, and identified common clinical manifestations, pathogenic genes, and variants. We also described the phenotypic differences across patients worldwide and among different BBS-associated genes. This study involved the largest cohort of Chinese patients with BBS, and provides new insights into the distinctive clinical features of specific pathogenic variants.
METHODS: Twenty Chinese patients diagnosed with BBS were enrolled in this study. We compared the phenotypes of Chinese BBS patients in this study with those from other countries to analyze the phenotypic differences across patients worldwide. In addition, genotype-phenotype correlations were described for our cohort. We also summarized all previously reported cases of BBS in Chinese patients (71 patients) and identified common and specific genetic variants in the Chinese population.
RESULTS: Twenty-eight variants, of which 10 are novel, in 5 different BBS-associated genes were identified in 20 Chinese BBS patients. By comparing the phenotypes of BBSome-coding genes (BBS2,7,9) with those of chaperonin-coding genes (BBS10,12), we found that patients with mutations in BBS10 and 12 had an earlier age of onset (1.10 Vs. 2.20, p < 0.01) and diagnosis (4.64 Vs. 13.17, p < 0.01), whereas patients with mutations in BBS2, 7, and 9 had a higher body mass index (28.35 Vs. 24.21, p < 0.05) and more vision problems (p < 0.05). Furthermore, in 91 Chinese BBS patients, mutations were predominant in BBS2 (28.89%) and BBS7 (15.56%), and the most frequent variants were in BBS2: c.534 + 1G > T (10/182 alleles) and BBS7: c.1002delT (7/182 alleles), marking a difference from the genotypic spectra of BBS reported abroad.
CONCLUSIONS: We recruited 20 Chinese patients with BBS for genetic and phenotypic analyses, and identified common clinical manifestations, pathogenic genes, and variants. We also described the phenotypic differences across patients worldwide and among different BBS-associated genes. This study involved the largest cohort of Chinese patients with BBS, and provides new insights into the distinctive clinical features of specific pathogenic variants.
摘要：
背景：Bardet-Biedl综合征（BBS）是一种非运动性纤毛病。迄今为止,已报导26个基因与BBS有关。然而,BBS是遗传异质性的，与其他纤毛病变有显著的临床重叠，使诊断复杂化。BBS患者的残疾和死亡率很高；因此，迫切需要提高我们对BBS的认识。因此，我们的研究旨在描述中国BBS的基因型和表型谱，并阐明基因型与表型的相关性。
方法：本研究纳入20例确诊为BBS的中国患者。我们在这项研究中比较了中国BBS患者与其他国家患者的表型，以分析全球患者的表型差异。此外,我们描述了我们队列的基因型-表型相关性.我们还总结了以前报道的所有中国患者（71例）的BBS病例，并确定了中国人群中常见和特定的遗传变异。
结果：28种变体，其中10个是小说，在20例中国BBS患者中鉴定出5种不同的BBS相关基因。通过比较BBSome编码基因(BBS2,7,9)的表型与分子伴侣编码基因(BBS10,12)的表型,我们发现BBS10和12突变的患者发病年龄较早(1.10Vs.2.20，p<0.01）和诊断（4.64Vs。13.17，p<0.01)，而具有BBS2、7和9突变的患者的体重指数较高(28.35Vs.24.21，p<0.05）和更多的视力问题（p<0.05）。此外，在91名中国BBS患者中，在BBS2(28.89%)和BBS7(15.56%)中,最常见的变异是BBS2：c.534+1G>T（10/182等位基因）和BBS7：c.1002delT（7/182等位基因），与国外报道的BBS基因型谱有差异。
结论：我们招募了20名中国BBS患者进行遗传和表型分析，并确定了常见的临床表现，致病基因，和变体。我们还描述了全球患者和不同BBS相关基因之间的表型差异。这项研究涉及中国最大的BBS患者队列，并为特定致病变异的独特临床特征提供了新的见解。
方法：本研究纳入20例确诊为BBS的中国患者。我们在这项研究中比较了中国BBS患者与其他国家患者的表型，以分析全球患者的表型差异。此外,我们描述了我们队列的基因型-表型相关性.我们还总结了以前报道的所有中国患者（71例）的BBS病例，并确定了中国人群中常见和特定的遗传变异。
结果：28种变体，其中10个是小说，在20例中国BBS患者中鉴定出5种不同的BBS相关基因。通过比较BBSome编码基因(BBS2,7,9)的表型与分子伴侣编码基因(BBS10,12)的表型,我们发现BBS10和12突变的患者发病年龄较早(1.10Vs.2.20，p<0.01）和诊断（4.64Vs。13.17，p<0.01)，而具有BBS2、7和9突变的患者的体重指数较高(28.35Vs.24.21，p<0.05）和更多的视力问题（p<0.05）。此外，在91名中国BBS患者中，在BBS2(28.89%)和BBS7(15.56%)中,最常见的变异是BBS2：c.534+1G>T（10/182等位基因）和BBS7：c.1002delT（7/182等位基因），与国外报道的BBS基因型谱有差异。
结论：我们招募了20名中国BBS患者进行遗传和表型分析，并确定了常见的临床表现，致病基因，和变体。我们还描述了全球患者和不同BBS相关基因之间的表型差异。这项研究涉及中国最大的BBS患者队列，并为特定致病变异的独特临床特征提供了新的见解。
