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A Novel GEMIN4 Variant in a Consanguineous Family Leads to Neurodevelopmental Impairment with Severe Microcephaly, Spastic Quadriplegia, Epilepsy, and Cataracts

Pathogenic variants in GEMIN4 contribute to a hereditary disorder characterized by neurodevelopmental features, microcephaly, cataracts, and renal abnormalities (known as NEDMCR). To date, only two homoallelic variations have been linked to the disease. Moreover, clinical features associated with th...

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Autores principales: Aldhalaan, Hesham, AlBakheet, Albandary, AlRuways, Sarah, AlMutairi, Nouf, AlNakiyah, Maha, AlGhofaili, Reema, Cardona-Londoño, Kelly J., Alahmadi, Khalid Omar, AlQudairy, Hanan, AlRasheed, Maha M., Colak, Dilek, Arold, Stefan T., Kaya, Namik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774908/
https://www.ncbi.nlm.nih.gov/pubmed/35052432
http://dx.doi.org/10.3390/genes13010092
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author Aldhalaan, Hesham
AlBakheet, Albandary
AlRuways, Sarah
AlMutairi, Nouf
AlNakiyah, Maha
AlGhofaili, Reema
Cardona-Londoño, Kelly J.
Alahmadi, Khalid Omar
AlQudairy, Hanan
AlRasheed, Maha M.
Colak, Dilek
Arold, Stefan T.
Kaya, Namik
author_facet Aldhalaan, Hesham
AlBakheet, Albandary
AlRuways, Sarah
AlMutairi, Nouf
AlNakiyah, Maha
AlGhofaili, Reema
Cardona-Londoño, Kelly J.
Alahmadi, Khalid Omar
AlQudairy, Hanan
AlRasheed, Maha M.
Colak, Dilek
Arold, Stefan T.
Kaya, Namik
author_sort Aldhalaan, Hesham
collection PubMed
description Pathogenic variants in GEMIN4 contribute to a hereditary disorder characterized by neurodevelopmental features, microcephaly, cataracts, and renal abnormalities (known as NEDMCR). To date, only two homoallelic variations have been linked to the disease. Moreover, clinical features associated with the variants have not been fully elucidated yet. Here, we identified a novel variant in GEMIN4 (NM_015721:exon2:c.440A>G:p.His147Arg) in two siblings from a consanguineous Saudi family by using whole exome sequencing followed by Sanger sequence verification. We comprehensively investigated the patients’ clinical features, including brain imaging and electroencephalogram findings, and compared their phenotypic characteristics with those of previously reported cases. In silico prediction and structural modeling support that the p.His147Arg variant is pathogenic.
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spelling pubmed-87749082022-01-21 A Novel GEMIN4 Variant in a Consanguineous Family Leads to Neurodevelopmental Impairment with Severe Microcephaly, Spastic Quadriplegia, Epilepsy, and Cataracts Aldhalaan, Hesham AlBakheet, Albandary AlRuways, Sarah AlMutairi, Nouf AlNakiyah, Maha AlGhofaili, Reema Cardona-Londoño, Kelly J. Alahmadi, Khalid Omar AlQudairy, Hanan AlRasheed, Maha M. Colak, Dilek Arold, Stefan T. Kaya, Namik Genes (Basel) Article Pathogenic variants in GEMIN4 contribute to a hereditary disorder characterized by neurodevelopmental features, microcephaly, cataracts, and renal abnormalities (known as NEDMCR). To date, only two homoallelic variations have been linked to the disease. Moreover, clinical features associated with the variants have not been fully elucidated yet. Here, we identified a novel variant in GEMIN4 (NM_015721:exon2:c.440A>G:p.His147Arg) in two siblings from a consanguineous Saudi family by using whole exome sequencing followed by Sanger sequence verification. We comprehensively investigated the patients’ clinical features, including brain imaging and electroencephalogram findings, and compared their phenotypic characteristics with those of previously reported cases. In silico prediction and structural modeling support that the p.His147Arg variant is pathogenic. MDPI 2021-12-30 /pmc/articles/PMC8774908/ /pubmed/35052432 http://dx.doi.org/10.3390/genes13010092 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Aldhalaan, Hesham
AlBakheet, Albandary
AlRuways, Sarah
AlMutairi, Nouf
AlNakiyah, Maha
AlGhofaili, Reema
Cardona-Londoño, Kelly J.
Alahmadi, Khalid Omar
AlQudairy, Hanan
AlRasheed, Maha M.
Colak, Dilek
Arold, Stefan T.
Kaya, Namik
A Novel GEMIN4 Variant in a Consanguineous Family Leads to Neurodevelopmental Impairment with Severe Microcephaly, Spastic Quadriplegia, Epilepsy, and Cataracts
title A Novel GEMIN4 Variant in a Consanguineous Family Leads to Neurodevelopmental Impairment with Severe Microcephaly, Spastic Quadriplegia, Epilepsy, and Cataracts
title_full A Novel GEMIN4 Variant in a Consanguineous Family Leads to Neurodevelopmental Impairment with Severe Microcephaly, Spastic Quadriplegia, Epilepsy, and Cataracts
title_fullStr A Novel GEMIN4 Variant in a Consanguineous Family Leads to Neurodevelopmental Impairment with Severe Microcephaly, Spastic Quadriplegia, Epilepsy, and Cataracts
title_full_unstemmed A Novel GEMIN4 Variant in a Consanguineous Family Leads to Neurodevelopmental Impairment with Severe Microcephaly, Spastic Quadriplegia, Epilepsy, and Cataracts
title_short A Novel GEMIN4 Variant in a Consanguineous Family Leads to Neurodevelopmental Impairment with Severe Microcephaly, Spastic Quadriplegia, Epilepsy, and Cataracts
title_sort novel gemin4 variant in a consanguineous family leads to neurodevelopmental impairment with severe microcephaly, spastic quadriplegia, epilepsy, and cataracts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774908/
https://www.ncbi.nlm.nih.gov/pubmed/35052432
http://dx.doi.org/10.3390/genes13010092
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