Department of Nephrology, Qilu Hospital, Shandong University, Jinan, China.
Department of Nephrology, Jining NO.1 People's Hospital, Jining, China.
Orphanet J Rare Dis. 2023 Aug 29;18(1):250. doi: 10.1186/s13023-023-02874-4.
Townes-Brocks syndrome is a rare autosomal dominant genetic syndrome caused by mutations in SALL1. The clinical features of Townes-Brocks syndrome are highly heterogonous. Identification of new SALL1 mutations and study of the relation between SALL1 mutations and clinical features can facilitate diagnosis of Townes-Brocks syndrome.
We collected clinical data and blood samples of the two patients and their family members for whole-exome sequencing and Sanger sequencing. Prediction analysis of the SALL1variation protein structure was achieved using Alphafold. The clinical materials and gene sequencing results were analyzed. The clinical materials and gene sequencing results were analyzed. The related literature of Townes-Brocks syndrome were searched and the genotype-renal phenotype analysis was performed combined with this two cases.
Based on the clinical features and gene sequencing results, the two patients were diagnosed as Townes-Brocks syndrome. Two novel SALL1 mutations (c.878-887del and c.1240G > T) were identified, both of which were pathogenic mutations. The correlation between genotypes and renal phenotypes in Townes-Brocks syndrome patients caused by SALL1 mutation were summarized.
This study identified two novel mutations and provided new insights into the correlation of genotypes and renal phenotypes of Townes-Brocks syndrome.
唐氏-布鲁克斯综合征是一种罕见的常染色体显性遗传综合征，由 SALL1 基因突变引起。唐氏-布鲁克斯综合征的临床特征高度异质。鉴定新的 SALL1 突变并研究 SALL1 突变与临床特征之间的关系，有助于唐氏-布鲁克斯综合征的诊断。
我们收集了两位患者及其家系成员的临床资料和血样，进行全外显子组测序和 Sanger 测序。使用 Alphafold 对 SALL1 变异蛋白结构进行预测分析。分析临床资料和基因测序结果。检索唐氏-布鲁克斯综合征的相关文献，并结合这两例患者进行基因型-肾表型分析。
根据临床特征和基因测序结果，两位患者被诊断为唐氏-布鲁克斯综合征。发现了两个新的 SALL1 突变（c.878-887del 和 c.1240G>T），均为致病性突变。总结了 SALL1 突变引起的唐氏-布鲁克斯综合征患者基因型与肾表型的相关性。
本研究鉴定了两个新的突变，为唐氏-布鲁克斯综合征的基因型与肾表型相关性提供了新的见解。
