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Two Cases of Recessive Intellectual Disability Caused by NDST1 and METTL23 Variants

Intellectual disability (ID) is a highly heterogeneous genetic condition with more than a thousand genes described so far. By exome sequencing of two consanguineous families presenting hallmark features of ID, we identified two homozygous variants in two genes previously associated with autosomal re...

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Autores principales: Khan, Amjad, Miao, Zhichao, Umair, Muhammad, Ullah, Amir, Alshabeeb, Mohammad A., Bilal, Muhammad, Ahmad, Farooq, Rappold, Gudrun A., Ansar, Muhammad, Carapito, Raphael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563614/
https://www.ncbi.nlm.nih.gov/pubmed/32878022
http://dx.doi.org/10.3390/genes11091021
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author Khan, Amjad
Miao, Zhichao
Umair, Muhammad
Ullah, Amir
Alshabeeb, Mohammad A.
Bilal, Muhammad
Ahmad, Farooq
Rappold, Gudrun A.
Ansar, Muhammad
Carapito, Raphael
author_facet Khan, Amjad
Miao, Zhichao
Umair, Muhammad
Ullah, Amir
Alshabeeb, Mohammad A.
Bilal, Muhammad
Ahmad, Farooq
Rappold, Gudrun A.
Ansar, Muhammad
Carapito, Raphael
author_sort Khan, Amjad
collection PubMed
description Intellectual disability (ID) is a highly heterogeneous genetic condition with more than a thousand genes described so far. By exome sequencing of two consanguineous families presenting hallmark features of ID, we identified two homozygous variants in two genes previously associated with autosomal recessive ID: NDST1 (c.1966G>A; p.Asp656Asn) and METTL23 (c.310T>C; p.Phe104Leu). The segregation of the variants was validated by Sanger sequencing in all family members. In silico homology modeling of wild-type and mutated proteins revealed substantial changes in the secondary structure of both proteins, indicating a possible effect on function. The identification and validation of new pathogenic NDST1 and METTL23 variants in two cases of autosomal recessive ID further highlight the importance of these genes in proper brain function and development.
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spelling pubmed-75636142020-10-27 Two Cases of Recessive Intellectual Disability Caused by NDST1 and METTL23 Variants Khan, Amjad Miao, Zhichao Umair, Muhammad Ullah, Amir Alshabeeb, Mohammad A. Bilal, Muhammad Ahmad, Farooq Rappold, Gudrun A. Ansar, Muhammad Carapito, Raphael Genes (Basel) Case Report Intellectual disability (ID) is a highly heterogeneous genetic condition with more than a thousand genes described so far. By exome sequencing of two consanguineous families presenting hallmark features of ID, we identified two homozygous variants in two genes previously associated with autosomal recessive ID: NDST1 (c.1966G>A; p.Asp656Asn) and METTL23 (c.310T>C; p.Phe104Leu). The segregation of the variants was validated by Sanger sequencing in all family members. In silico homology modeling of wild-type and mutated proteins revealed substantial changes in the secondary structure of both proteins, indicating a possible effect on function. The identification and validation of new pathogenic NDST1 and METTL23 variants in two cases of autosomal recessive ID further highlight the importance of these genes in proper brain function and development. MDPI 2020-08-31 /pmc/articles/PMC7563614/ /pubmed/32878022 http://dx.doi.org/10.3390/genes11091021 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Khan, Amjad
Miao, Zhichao
Umair, Muhammad
Ullah, Amir
Alshabeeb, Mohammad A.
Bilal, Muhammad
Ahmad, Farooq
Rappold, Gudrun A.
Ansar, Muhammad
Carapito, Raphael
Two Cases of Recessive Intellectual Disability Caused by NDST1 and METTL23 Variants
title Two Cases of Recessive Intellectual Disability Caused by NDST1 and METTL23 Variants
title_full Two Cases of Recessive Intellectual Disability Caused by NDST1 and METTL23 Variants
title_fullStr Two Cases of Recessive Intellectual Disability Caused by NDST1 and METTL23 Variants
title_full_unstemmed Two Cases of Recessive Intellectual Disability Caused by NDST1 and METTL23 Variants
title_short Two Cases of Recessive Intellectual Disability Caused by NDST1 and METTL23 Variants
title_sort two cases of recessive intellectual disability caused by ndst1 and mettl23 variants
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563614/
https://www.ncbi.nlm.nih.gov/pubmed/32878022
http://dx.doi.org/10.3390/genes11091021
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