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TAB2 deletions and variants cause a highly recognisable syndrome with mitral valve disease, cardiomyopathy, short stature and hypermobility.
Engwerda, Aafke; Leenders, Erika K S M; Frentz, Barbara; Terhal, Paulien A; Löhner, Katharina; de Vries, Bert B A; Dijkhuizen, Trijnie; Vos, Yvonne J; Rinne, Tuula; van den Berg, Maarten P; Roofthooft, Marc T R; Deelen, Patrick; van Ravenswaaij-Arts, Conny M A; Kerstjens-Frederikse, Wilhelmina S.
Afiliación
  • Engwerda A; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Leenders EKSM; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Frentz B; Vanboeijen, Assen, The Netherlands.
  • Terhal PA; Department of Genetics, Utrecht University Medical Center, Utrecht, The Netherlands.
  • Löhner K; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • de Vries BBA; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Dijkhuizen T; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Vos YJ; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Rinne T; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
  • van den Berg MP; Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Roofthooft MTR; Department of Paediatric Cardiology, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, The Netherlands.
  • Deelen P; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • van Ravenswaaij-Arts CMA; Department of Genetics, Utrecht University Medical Center, Utrecht, The Netherlands.
  • Kerstjens-Frederikse WS; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Eur J Hum Genet ; 29(11): 1669-1676, 2021 11.
Article en En | MEDLINE | ID: mdl-34456334
Deletions that include the gene TAB2 and TAB2 loss-of-function variants have previously been associated with congenital heart defects and cardiomyopathy. However, other features, including short stature, facial dysmorphisms, connective tissue abnormalities and a variable degree of developmental delay, have only been mentioned occasionally in literature and thus far not linked to TAB2. In a large-scale, social media-based chromosome 6 study, we observed a shared phenotype in patients with a 6q25.1 deletion that includes TAB2. To confirm if this phenotype is caused by haploinsufficiency of TAB2 and to delineate a TAB2-related phenotype, we subsequently sequenced TAB2 in patients with matching phenotypes and recruited patients with pathogenic TAB2 variants detected by exome sequencing. This identified 11 patients with a deletion containing TAB2 (size 1.68-14.31 Mb) and 14 patients from six families with novel truncating TAB2 variants. Twenty (80%) patients had cardiac disease, often mitral valve defects and/or cardiomyopathy, 18 (72%) had short stature and 18 (72%) had hypermobility. Twenty patients (80%) had facial features suggestive for Noonan syndrome. No substantial phenotypic differences were noted between patients with deletions and those with intragenic variants. We then compared our patients to 45 patients from the literature. All literature patients had cardiac diseases, but syndromic features were reported infrequently. Our study shows that the phenotype in 6q25.1 deletions is caused by haploinsufficiency of TAB2 and that TAB2 is associated not just with cardiac disease, but also with a distinct phenotype, with features overlapping with Noonan syndrome. We propose the name "TAB2-related syndrome".
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenotipo / Proteínas Adaptadoras Transductoras de Señales / Enanismo / Enfermedades de las Válvulas Cardíacas / Inestabilidad de la Articulación / Cardiomiopatías Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Eur J Hum Genet Asunto de la revista: GENETICA MEDICA Año: 2021 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenotipo / Proteínas Adaptadoras Transductoras de Señales / Enanismo / Enfermedades de las Válvulas Cardíacas / Inestabilidad de la Articulación / Cardiomiopatías Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Eur J Hum Genet Asunto de la revista: GENETICA MEDICA Año: 2021 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido