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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mosby 2013
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.
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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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