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A novel variant of C12orf4 in a consanguineous Armenian family confirms the etiology of autosomal recessive intellectual disability type 66 with delineation of the phenotype

BACKGROUND: Intellectual disability (ID) is a feature of many rare diseases caused by thousands of genes. This genetic heterogeneity implies that pathogenic variants in a specific gene are found only in a small number of patients, and difficulties arise in the definition of prevailing genotype and c...

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Autores principales: Hancarova, Miroslava, Babikyan, Davit, Bendova, Sarka, Midyan, Susanna, Prchalova, Darina, Shahsuvaryan, Gohar, Stranecky, Viktor, Sarkisian, Tamara, Sedlacek, Zdenek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732288/
https://www.ncbi.nlm.nih.gov/pubmed/31334606
http://dx.doi.org/10.1002/mgg3.865
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author Hancarova, Miroslava
Babikyan, Davit
Bendova, Sarka
Midyan, Susanna
Prchalova, Darina
Shahsuvaryan, Gohar
Stranecky, Viktor
Sarkisian, Tamara
Sedlacek, Zdenek
author_facet Hancarova, Miroslava
Babikyan, Davit
Bendova, Sarka
Midyan, Susanna
Prchalova, Darina
Shahsuvaryan, Gohar
Stranecky, Viktor
Sarkisian, Tamara
Sedlacek, Zdenek
author_sort Hancarova, Miroslava
collection PubMed
description BACKGROUND: Intellectual disability (ID) is a feature of many rare diseases caused by thousands of genes. This genetic heterogeneity implies that pathogenic variants in a specific gene are found only in a small number of patients, and difficulties arise in the definition of prevailing genotype and characteristic phenotype associated with that gene. One of such very rare disorders is autosomal recessive ID type 66 (OMIM #618221) caused by defects in C12orf4. Up to now, six families have been reported with mostly truncating variants. The spectrum of the clinical phenotype was not emphasized in previous reports, and detailed phenotype was not always available from previous patients, especially from large cohort studies. METHODS: Exome sequencing was performed in a consanguineous Armenian family with two affected adult brothers. RESULTS: The patients carry a novel homozygous nonsense C12orf4 variant. The integration of previous data and phenotyping of the brothers indicate that the clinical picture of C12orf4 defects involves hypotonia in infancy, rather severe ID, speech impairment, and behavioral problems such as aggressiveness, unstable mood, and autistic features. Several other symptoms are more variable and less consistent. CONCLUSION: This rather nonsyndromic and nonspecific clinical picture implies that additional patients with C12orf4 defects will likely continue to be identified using the “genotype‐first” approach, rather than based on clinical assessment. The phenotype needs further delineation in future reports.
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spelling pubmed-67322882019-09-12 A novel variant of C12orf4 in a consanguineous Armenian family confirms the etiology of autosomal recessive intellectual disability type 66 with delineation of the phenotype Hancarova, Miroslava Babikyan, Davit Bendova, Sarka Midyan, Susanna Prchalova, Darina Shahsuvaryan, Gohar Stranecky, Viktor Sarkisian, Tamara Sedlacek, Zdenek Mol Genet Genomic Med Clinical Reports BACKGROUND: Intellectual disability (ID) is a feature of many rare diseases caused by thousands of genes. This genetic heterogeneity implies that pathogenic variants in a specific gene are found only in a small number of patients, and difficulties arise in the definition of prevailing genotype and characteristic phenotype associated with that gene. One of such very rare disorders is autosomal recessive ID type 66 (OMIM #618221) caused by defects in C12orf4. Up to now, six families have been reported with mostly truncating variants. The spectrum of the clinical phenotype was not emphasized in previous reports, and detailed phenotype was not always available from previous patients, especially from large cohort studies. METHODS: Exome sequencing was performed in a consanguineous Armenian family with two affected adult brothers. RESULTS: The patients carry a novel homozygous nonsense C12orf4 variant. The integration of previous data and phenotyping of the brothers indicate that the clinical picture of C12orf4 defects involves hypotonia in infancy, rather severe ID, speech impairment, and behavioral problems such as aggressiveness, unstable mood, and autistic features. Several other symptoms are more variable and less consistent. CONCLUSION: This rather nonsyndromic and nonspecific clinical picture implies that additional patients with C12orf4 defects will likely continue to be identified using the “genotype‐first” approach, rather than based on clinical assessment. The phenotype needs further delineation in future reports. John Wiley and Sons Inc. 2019-07-23 /pmc/articles/PMC6732288/ /pubmed/31334606 http://dx.doi.org/10.1002/mgg3.865 Text en © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Clinical Reports
Hancarova, Miroslava
Babikyan, Davit
Bendova, Sarka
Midyan, Susanna
Prchalova, Darina
Shahsuvaryan, Gohar
Stranecky, Viktor
Sarkisian, Tamara
Sedlacek, Zdenek
A novel variant of C12orf4 in a consanguineous Armenian family confirms the etiology of autosomal recessive intellectual disability type 66 with delineation of the phenotype
title A novel variant of C12orf4 in a consanguineous Armenian family confirms the etiology of autosomal recessive intellectual disability type 66 with delineation of the phenotype
title_full A novel variant of C12orf4 in a consanguineous Armenian family confirms the etiology of autosomal recessive intellectual disability type 66 with delineation of the phenotype
title_fullStr A novel variant of C12orf4 in a consanguineous Armenian family confirms the etiology of autosomal recessive intellectual disability type 66 with delineation of the phenotype
title_full_unstemmed A novel variant of C12orf4 in a consanguineous Armenian family confirms the etiology of autosomal recessive intellectual disability type 66 with delineation of the phenotype
title_short A novel variant of C12orf4 in a consanguineous Armenian family confirms the etiology of autosomal recessive intellectual disability type 66 with delineation of the phenotype
title_sort novel variant of c12orf4 in a consanguineous armenian family confirms the etiology of autosomal recessive intellectual disability type 66 with delineation of the phenotype
topic Clinical Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732288/
https://www.ncbi.nlm.nih.gov/pubmed/31334606
http://dx.doi.org/10.1002/mgg3.865
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