Townes-Brocks syndrome: genotype-phenotype correlations of SALL1 variants in our series and the literature

Townes-Brocks syndrome (TBS, MIM#107480) is an autosomal dominant disorder linked to SALL1 alterations and characterized by a clinical triad (anorectal, thumb, and external-ear malformations), along with variable features. Renal failure and deafness can occur at any age, making follow-up essential. Some genotype-phenotype correlations have been suggested but data are limited. We collected clinical and molecular data from 49 patients with a SALL1 (likely) pathogenic variant identified in our laboratory or through collaborations, and reviewed the 207 SALL1 related-TBS patients previously reported in the literature. We performed statistical analysis to study genotype-phenotype correlations based notably on the variant position in relation to the glutamine-rich region. In our series, 25% of individuals presented with the clinical triad compared to 49.7% in the literature. The deafness frequency was similar (65%). Renal failure was diagnosed in 39.6% of our patients compared to 29.3% in the literature. Developmental delay or intellectual disability affected 9% of patients. Of the 22 SALL1 variants in our series, 35% were located upstream of the glutamine-rich region, compared to 6.5% in the literature. Statistical analysis was performed on all patients, of which 26 and 200 carried a variant upstream and downstream of the glutamine-rich region, respectively. A significant increase in deafness, dysplastic ear, and thumb malformations and a significant decrease in renal failure were observed in the individuals carrying a variant located downstream of the region, but the patients were significantly younger. Future studies should aim to elucidate the complex pathophysiological mechanisms and prognosis of TBS, functionally and prospectively.

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Journal
European Journal of Human Genetics
Published
2025-05-10
DOI
https://doi.org/10.1038/s41431-025-01855-4
Citations
1
Primary Topic
Renal and related cancers
Type
article
Field-Weighted Citation Impact
0.81

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article

Townes-Brocks syndrome: genotype-phenotype correlations of SALL1 variants in our series and the literature

Aurélie Mezel, Laurence Bellengier, Nassima Ramdane, Perrine Brunelle et al.
1 citations
European Journal of Human Genetics
Renal and related cancers
0.81
article

Townes-Brocks syndrome: genotype-phenotype correlations of SALL1 variants in our series and the literature

Aurélie Mezel, Laurence Bellengier, Nassima Ramdane, Perrine Brunelle, Robert Sfeir, Catherine Vincent-Delorme, P. Toulemonde, Fiona Leduc, Christine Lefèvre, Fabienne Escande, Charlotte Samaille, Léa Giacomello
article en
1 citations

Abstract

Townes-Brocks syndrome (TBS, MIM#107480) is an autosomal dominant disorder linked to SALL1 alterations and characterized by a clinical triad (anorectal, thumb, and external-ear malformations), along with variable features. Renal failure and deafness can occur at any age, making follow-up essential. Some genotype-phenotype correlations have been suggested but data are limited. We collected clinical and molecular data from 49 patients with a SALL1 (likely) pathogenic variant identified in our laboratory or through collaborations, and reviewed the 207 SALL1 related-TBS patients previously reported in the literature. We performed statistical analysis to study genotype-phenotype correlations based notably on the variant position in relation to the glutamine-rich region. In our series, 25% of individuals presented with the clinical triad compared to 49.7% in the literature. The deafness frequency was similar (65%). Renal failure was diagnosed in 39.6% of our patients compared to 29.3% in the literature. Developmental delay or intellectual disability affected 9% of patients. Of the 22 SALL1 variants in our series, 35% were located upstream of the glutamine-rich region, compared to 6.5% in the literature. Statistical analysis was performed on all patients, of which 26 and 200 carried a variant upstream and downstream of the glutamine-rich region, respectively. A significant increase in deafness, dysplastic ear, and thumb malformations and a significant decrease in renal failure were observed in the individuals carrying a variant located downstream of the region, but the patients were significantly younger. Future studies should aim to elucidate the complex pathophysiological mechanisms and prognosis of TBS, functionally and prospectively.

European Journal of Human GeneticsVol. 33(11)
Université Libre de Bruxelles (BE), Nottingham University Hospitals NHS Trust (GB), Vrije Universiteit Brussel (BE), Inserm (FR), Université Paris Cité (FR), Université de Lille (FR), Great Ormond Street Hospital (GB), Centre Hospitalier Universitaire de Grenoble (FR), St George’s University Hospitals NHS Foundation Trust (GB), Turku University Hospital (FI), Nottingham City Hospital (GB), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Nice (FR), Sorbonne Université (FR), Institut Necker Enfants Malades (FR), Hôpital Armand-Trousseau (FR), Lille’s Cardiology Hospital (FR), Centre Hospitalier Universitaire de Tours (FR), Assistance Publique – Hôpitaux de Paris (FR), Institut Régional de Médecine Physique et de Réadaptation (FR), Centre Hospitalier Régional et Universitaire de Nancy (FR), Hospices Civils de Lyon (FR), Hôpital Jeanne de Flandre (FR), Normandie Université (FR), Queen Fabiola Children's University Hospital (BE), Laboratoire de Physique Corpusculaire de Caen (FR), Hôpital Pellegrin (FR), St George's Hospital (GB), Centre Hospitalier Universitaire de Caen Normandie (FR), Maison des Sciences sociales et des Humanités Ange Guépin (FR), Centre Hospitalier du Mans (FR), Groupe Hospitalier de l'Institut Catholique de Lille (FR), Génétique Médicale & Génomique Fonctionelle (FR), Institut pour l'avancée des biosciences (FR), Hôpital de la Timone (FR), Institut de Biologie de Lille (FR), Nutrition-Génétique et Exposition aux Risques Environnementaux (FR), University College London (GB), Université de Rouen Normandie (FR), Université Grenoble Alpes (FR), Université de Lorraine (FR), Université de Caen Normandie (FR)
Centre hospitalier régional universitaire de Lille
Quality Education
Openalex Percentile: Top 28%
Renal and related cancers
0.81
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