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Homozygous SALL1 Mutation Causes a Novel Multiple Congenital Anomaly—Mental Retardation Syndrome
OBJECTIVE: To delineate a novel autosomal recessive multiple congenital anomaly-mental retardation (MCA-MR) syndrome in 2 female siblings of a consanguineous pedigree and to identify the disease-causing mutation. STUDY DESIGN: Both siblings were clinically characterized and homozygosity mapping and...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Mosby
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757162/ https://www.ncbi.nlm.nih.gov/pubmed/23069192 http://dx.doi.org/10.1016/j.jpeds.2012.08.042 |
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author | Vodopiutz, Julia Zoller, Heinz Fenwick, Aimée L. Arnhold, Richard Schmid, Max Prayer, Daniela Müller, Thomas Repa, Andreas Pollak, Arnold Aufricht, Christoph Wilkie, Andrew O.M. Janecke, Andreas R. |
author_facet | Vodopiutz, Julia Zoller, Heinz Fenwick, Aimée L. Arnhold, Richard Schmid, Max Prayer, Daniela Müller, Thomas Repa, Andreas Pollak, Arnold Aufricht, Christoph Wilkie, Andrew O.M. Janecke, Andreas R. |
author_sort | Vodopiutz, Julia |
collection | PubMed |
description | OBJECTIVE: To delineate a novel autosomal recessive multiple congenital anomaly-mental retardation (MCA-MR) syndrome in 2 female siblings of a consanguineous pedigree and to identify the disease-causing mutation. STUDY DESIGN: Both siblings were clinically characterized and homozygosity mapping and sequencing of candidate genes were applied. The contribution of nonsense-mediated messenger RNA (mRNA) decay to the expression of mutant mRNA in fibroblasts of a healthy carrier and a control was studied by pyrosequencing. RESULTS: We identified the first homozygous SALL1 mutation, c.3160C > T (p.R1054*), in 2 female siblings presenting with multiple congenital anomalies, central nervous system defects, cortical blindness, and absence of psychomotor development (ie, a novel recognizable, autosomal recessive MCA-MR). The mutant SALL1 transcript partially undergoes nonsense-mediated mRNA decay and is present at 43% of the normal transcript level in the fibroblasts of a healthy carrier. CONCLUSION: Previously heterozygous SALL1 mutations and deletions have been associated with dominantly inherited anal-renal-radial-ear developmental anomalies. We identified an allelic recessive SALL1-related MCA-MR. Our findings imply that quantity and quality of SALL1 transcript are important for SALL1 function and determine phenotype, and mode of inheritance, of allelic SALL1-related disorders. This novel MCA-MR emphasizes SALL1 function as critical for normal central nervous system development and warrants a detailed neurologic investigation in all individuals with SALL1 mutations. |
format | Online Article Text |
id | pubmed-3757162 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Mosby |
record_format | MEDLINE/PubMed |
spelling | pubmed-37571622013-08-30 Homozygous SALL1 Mutation Causes a Novel Multiple Congenital Anomaly—Mental Retardation Syndrome Vodopiutz, Julia Zoller, Heinz Fenwick, Aimée L. Arnhold, Richard Schmid, Max Prayer, Daniela Müller, Thomas Repa, Andreas Pollak, Arnold Aufricht, Christoph Wilkie, Andrew O.M. Janecke, Andreas R. J Pediatr Original Article OBJECTIVE: To delineate a novel autosomal recessive multiple congenital anomaly-mental retardation (MCA-MR) syndrome in 2 female siblings of a consanguineous pedigree and to identify the disease-causing mutation. STUDY DESIGN: Both siblings were clinically characterized and homozygosity mapping and sequencing of candidate genes were applied. The contribution of nonsense-mediated messenger RNA (mRNA) decay to the expression of mutant mRNA in fibroblasts of a healthy carrier and a control was studied by pyrosequencing. RESULTS: We identified the first homozygous SALL1 mutation, c.3160C > T (p.R1054*), in 2 female siblings presenting with multiple congenital anomalies, central nervous system defects, cortical blindness, and absence of psychomotor development (ie, a novel recognizable, autosomal recessive MCA-MR). The mutant SALL1 transcript partially undergoes nonsense-mediated mRNA decay and is present at 43% of the normal transcript level in the fibroblasts of a healthy carrier. CONCLUSION: Previously heterozygous SALL1 mutations and deletions have been associated with dominantly inherited anal-renal-radial-ear developmental anomalies. We identified an allelic recessive SALL1-related MCA-MR. Our findings imply that quantity and quality of SALL1 transcript are important for SALL1 function and determine phenotype, and mode of inheritance, of allelic SALL1-related disorders. This novel MCA-MR emphasizes SALL1 function as critical for normal central nervous system development and warrants a detailed neurologic investigation in all individuals with SALL1 mutations. Mosby 2013-03 /pmc/articles/PMC3757162/ /pubmed/23069192 http://dx.doi.org/10.1016/j.jpeds.2012.08.042 Text en © 2013 Mosby, Inc. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license |
spellingShingle | Original Article Vodopiutz, Julia Zoller, Heinz Fenwick, Aimée L. Arnhold, Richard Schmid, Max Prayer, Daniela Müller, Thomas Repa, Andreas Pollak, Arnold Aufricht, Christoph Wilkie, Andrew O.M. Janecke, Andreas R. Homozygous SALL1 Mutation Causes a Novel Multiple Congenital Anomaly—Mental Retardation Syndrome |
title | Homozygous SALL1 Mutation Causes a Novel Multiple Congenital Anomaly—Mental Retardation Syndrome |
title_full | Homozygous SALL1 Mutation Causes a Novel Multiple Congenital Anomaly—Mental Retardation Syndrome |
title_fullStr | Homozygous SALL1 Mutation Causes a Novel Multiple Congenital Anomaly—Mental Retardation Syndrome |
title_full_unstemmed | Homozygous SALL1 Mutation Causes a Novel Multiple Congenital Anomaly—Mental Retardation Syndrome |
title_short | Homozygous SALL1 Mutation Causes a Novel Multiple Congenital Anomaly—Mental Retardation Syndrome |
title_sort | homozygous sall1 mutation causes a novel multiple congenital anomaly—mental retardation syndrome |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757162/ https://www.ncbi.nlm.nih.gov/pubmed/23069192 http://dx.doi.org/10.1016/j.jpeds.2012.08.042 |
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