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Expansion of phenotype and genotypic data in CRB2-related syndrome.
Lamont, Ryan E; Tan, Wen-Hann; Innes, A Micheil; Parboosingh, Jillian S; Schneidman-Duhovny, Dina; Rajkovic, Aleksandar; Pappas, John; Altschwager, Pablo; DeWard, Stephanie; Fulton, Anne; Gray, Kathryn J; Krall, Max; Mehta, Lakshmi; Rodan, Lance H; Saller, Devereux N; Steele, Deanna; Stein, Deborah; Yatsenko, Svetlana A; Bernier, François P; Slavotinek, Anne M.
Afiliación
  • Lamont RE; Department of Medical Genetics and Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
  • Tan WH; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
  • Innes AM; Department of Medical Genetics and Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
  • Parboosingh JS; Department of Medical Genetics and Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
  • Schneidman-Duhovny D; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
  • Rajkovic A; Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.
  • Pappas J; Center for Medical Genetics and Genomics, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
  • Altschwager P; Clinical Genetic Services, Department of Pediatrics, NYU School of Medicine, New York, NY, USA.
  • DeWard S; Department of Ophthalmology, Boston Children's Hospital, Boston, MA, USA.
  • Fulton A; Department of Ophthalmology, Pontificia Universidad Catolica de Chile, Santiago, Chile.
  • Gray KJ; GeneDx, Inc., Gaithersburg, MD, USA.
  • Krall M; Department of Ophthalmology, Boston Children's Hospital, Boston, MA, USA.
  • Mehta L; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
  • Rodan LH; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
  • Saller DN; Division of Medical Genetics, Icahn School of Medicine at Mount Sinai & Mount Sinai Medical Center, New York, NY, USA.
  • Steele D; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
  • Stein D; Center for Medical Genetics and Genomics, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
  • Yatsenko SA; Center for Medical Genetics and Genomics, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
  • Bernier FP; Division of Nephrology, Boston Children's Hospital, Boston, MA, USA.
  • Slavotinek AM; Center for Medical Genetics and Genomics, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Eur J Hum Genet ; 24(10): 1436-44, 2016 10.
Article en En | MEDLINE | ID: mdl-27004616
Sequence variants in CRB2 cause a syndrome with greatly elevated maternal serum alpha-fetoprotein and amniotic fluid alpha-fetoprotein levels, cerebral ventriculomegaly and renal findings similar to Finnish congenital nephrosis. All reported patients have been homozygotes or compound heterozygotes for sequence variants in the Crumbs, Drosophila, Homolog of, 2 (CRB2) genes. Variants affecting CRB2 function have also been identified in four families with steroid resistant nephrotic syndrome, but without any other known systemic findings. We ascertained five, previously unreported individuals with biallelic variants in CRB2 that were predicted to affect function. We compiled the clinical features of reported cases and reviewed available literature for cases with features suggestive of CRB2-related syndrome in order to better understand the phenotypic and genotypic manifestations. Phenotypic analyses showed that ventriculomegaly was a common clinical manifestation (9/11 confirmed cases), in contrast to the original reports, in which patients were ascertained due to renal disease. Two children had minor eye findings and one was diagnosed with a B-cell lymphoma. Further genetic analysis identified one family with two affected siblings who were both heterozygous for a variant in NPHS2 predicted to affect function and separate families with sequence variants in NPHS4 and BBS7 in addition to the CRB2 variants. Our report expands the clinical phenotype of CRB2-related syndrome and establishes ventriculomegaly and hydrocephalus as frequent manifestations. We found additional sequence variants in genes involved in kidney development and ciliopathies in patients with CRB2-related syndrome, suggesting that these variants may modify the phenotype.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenotipo / Proteínas Portadoras / Genotipo / Hidrocefalia / Proteínas de la Membrana / Nefrosis Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Female / Humans / Infant / Male Idioma: En Revista: Eur J Hum Genet Asunto de la revista: GENETICA MEDICA Año: 2016 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
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PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenotipo / Proteínas Portadoras / Genotipo / Hidrocefalia / Proteínas de la Membrana / Nefrosis Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Female / Humans / Infant / Male Idioma: En Revista: Eur J Hum Genet Asunto de la revista: GENETICA MEDICA Año: 2016 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido