Dataset Information

Identification of two novel SALL1 mutations in chinese families with townes-brocks syndrome and literature review.

ABSTRACT:

Background

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.

Methods

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.

Results

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.

Conclusion

This study identified two novel mutations and provided new insights into the correlation of genotypes and renal phenotypes of Townes-Brocks syndrome.

SUBMITTER: Wang Z

PROVIDER: S-EPMC10466882 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Identification of two novel SALL1 mutations in chinese families with townes-brocks syndrome and literature review.

Wang Zhendong Z Sun Zhenfu Z Diao Yujie Y Wang Zhouyang Z Yang Xiangdong X Jiang Bei B Wu Yumei Y Liu Guangyi G

Orphanet journal of rare diseases 20230829 1

<h4>Background</h4>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.<h4>Methods</h4>We collected clinical data and blood samples of the two patients and their family members for whole-exome sequencing and Sanger sequ ...[more]

PMID: 37644569

Similar Datasets

Project description:BackgroundTo investigate the functional characteristics of heterozygous variants in the SALL1 gene in two children with Townes-Brocks syndrome (TBS), as well as the underlying mechanisms leading to chronic kidney disease.MethodsWe retrospectively analyzed the clinical manifestations, laboratory findings, and genetic backgrounds of two TBS patients admitted to our hospital presenting with chronic kidney disease stage 2 and focal segmental glomerulosclerosis (FSGS). The genetic function was investigated through cultured cells transfected with variants. The Sall1 protein expression level was detected by western blotting. Immunofluorescence was also employed to detect the subcellular localization of SALL1.ResultsNovel heterozygous genetic variations (c.3175 C > T and c.694 C > T) were detected in two respective probands with distinct clinical presentations: Proband 1 presented with polydactyly, nephrotic syndrome, and stage 2 chronic kidney disease; while Proband 2 manifested renal dysplasia, progressive proteinuria, and also stage 2 chronic kidney disease. FSGS was confirmed by kidney biopsies from both probands. To assess the functional impact of these variations, we introduced mutant plasmids carrying the c.3175 C > T and c.694 C > T variants into podocytes. The expression level of variant c.3175 C > T(p.Q1059X) in podocytes showed a significant decrease compared to that of the wild-type (P < 0.05), whereas variant c.694 C > T(p.Q232X) was markedly upregulated (P < 0.01). Immunofluorescence analysis revealed aberrant localization patterns for both SALL1 variants within podocytes.ConclusionsTwo patients with Townes-Brocks syndrome (TBS) harboring novel variants presented atypical phenotypes, characterized primarily by significant and rapidly progressing renal involvement. Rare renal biopsy pathology revealed the presence of focal segmental glomerulosclerosis (FSGS) in both cases. Experimental validation demonstrated that both variants led to alterations in the molecular size, expression level, and localization of the Sall1 protein, suggesting that these SALL1 gene variants might contribute to FSGS by impacting podocyte function.

Project description:BackgroundPrevious studies have revealed that mutations of Spalt Like Transcription Factor 1 (SALL1) are responsible for Townes-Brocks syndrome (TBS), a rare genetic disorder that is characterized by an imperforate anus, dysplastic ears, thumb malformations and other abnormalities, such as hearing loss, foot malformations, renal impairment with or without renal malformations, genitourinary malformations, and congenital heart disease. In addition, the protein tyrosine phosphatase receptor type Q (PTPRQ) gene has been identified in nonsyndromic hearing loss patients with autosomal recessive or autosomal dominant inherited patterns.MethodsA Chinese family with TBS and hearing loss was enrolled in this study. The proband was a two-month-old girl who suffered from congenital anal atresia with rectal perineal fistula, ventricular septal defect, patent ductus arteriosus, pulmonary hypertension (PH), and finger deformities. The proband's father also had external ear deformity with deafness, toe deformities and PH, although his anus was normal. Further investigation found that the proband's mother presented nonsyndromic hearing loss, and the proband's mother's parents were consanguine married. Whole-exome sequencing and Sanger sequencing were applied to detect the genetic lesions of TBS and nonsyndromic hearing loss.ResultsVia whole-exome sequencing and Sanger sequencing of the proband and her mother, we identified a novel heterozygous mutation (ENST00000251020: c.1428_1429insT, p. K478QfsX38) of SALL1 in the proband and her father who presented TBS phenotypes, and we also detected a new homozygous mutation [ENST00000266688: c.1057_1057delC, p. L353SfsX8)] of PTPRQ in the proband's mother and uncle, who suffered from nonsyndromic hearing loss. Both mutations were located in the conserved sites of the respective protein and were predicted to be deleterious by informatics analysis.ConclusionsThis study confirmed the diagnosis of TBS at the molecular level and expanded the spectrum of SALL1 mutations and PTPRQ mutations. Our study may contribute to the clinical management and genetic counselling of TBS and hearing loss.

Dataset Information

Identification of two novel SALL1 mutations in chinese families with townes-brocks syndrome and literature review.

Background

Methods

Results

Conclusion

Publications

Identification of two novel SALL1 mutations in chinese families with townes-brocks syndrome and literature review.

Similar Datasets

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