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- Title
Diagnosis of Townes-Brocks Syndrome in a Turkish Adolescent with End-Stage Renal Failure.
- Authors
Yakubi, Mustafa; Dursun, İsmail; Dündar, Munis
- Abstract
Introduction: Townes-Brocks syndrome (TBS) is identified by a triad of imperforate anus, malformed ears, and thumb abnormalities. Additional associated features include renal complications, congenital heart abnormalities, foot abnormalities, and genitourinary malformations, and intellectual disability. Less common characteristics encompass iris coloboma, Duane anomaly, Arnold-Chiari malformation type 1, and developmental delay. Here we report a 15-year-old male patient with congenital hearing loss, global developmental delay, and the incidental discovery of chronic kidney disease. The patient's physical examination indicated TBS. However, clinical exon sequencing (CES) genetic testing revealed a pathogenic mutation in the SALL1 gene and confirmed the diagnosis. Methods: We took the patient for clinical exome sequencing. Results:CES analysis revealed a novel heterozygous likely pathogenic variant in SALL1 gene (NM_002968/3 c.1336_1370del p.(Phe446Leufs4)). We also detected a hemizygous likely pathogenic variant in the POU3F4 gene (NM_000307/5 c.478C>T p.(Gln160)), which could similarly lead to the patient's congenital deafness (OMIM #304400 Deafness, X-linked 2). This suspicion arose because the patient's cousin also has congenital hearing loss without any other anomalies. Thus, we have arranged for further genetic examination of the cousin. Conclusion: Our patient had a frameshift mutation in the hotspot region, leading to premature truncation. This resulted in a severe TBS phenotype with severe dental issues, which led to the extraction of teeth during childhood due to significant mouth deformities and functional problems. Recent studies have also emphasized that premature SALL1 protein truncation results in a more severe TBS phenotype due to a dominant negative effect.
- Subjects
TURKS; KIDNEY failure; CONGENITAL heart disease; ARNOLD-Chiari deformity; CHRONIC kidney failure; INTELLECTUAL disabilities
- Publication
Gazi Medical Journal, 2024, Vol 35, p52
- ISSN
1300-056X
- Publication type
Article