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Next generation sequencing reveals novel homozygous frameshift in PUS7 and splice acceptor variants in AASS gene leading to intellectual disability, developmental delay, dysmorphic feature and microcephaly

Intellectual developmental disorder with abnormal behavior, microcephaly and short stature (IDDABS), (OMIM# 618342) is an autosomal recessive condition described as developmental delay, poor or absent speech, intellectual disability, short stature, mild to progressive microcephaly, delayed psychomot...

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Autores principales: Naseer, Muhammad Imran, Abdulkareem, Angham Abdulrahman, Jan, Mohammed M., Chaudhary, Adeel G., Alharazy, Shatha, AlQahtani, Mohammad H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569139/
https://www.ncbi.nlm.nih.gov/pubmed/33100873
http://dx.doi.org/10.1016/j.sjbs.2020.09.033
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author Naseer, Muhammad Imran
Abdulkareem, Angham Abdulrahman
Jan, Mohammed M.
Chaudhary, Adeel G.
Alharazy, Shatha
AlQahtani, Mohammad H.
author_facet Naseer, Muhammad Imran
Abdulkareem, Angham Abdulrahman
Jan, Mohammed M.
Chaudhary, Adeel G.
Alharazy, Shatha
AlQahtani, Mohammad H.
author_sort Naseer, Muhammad Imran
collection PubMed
description Intellectual developmental disorder with abnormal behavior, microcephaly and short stature (IDDABS), (OMIM# 618342) is an autosomal recessive condition described as developmental delay, poor or absent speech, intellectual disability, short stature, mild to progressive microcephaly, delayed psychomotor development, hyperactivity, seizure, along with mild to swear aggressive behavior. Homozygous frameshift mutation in Pseudouridine Synthase 7, Putative; (PUS7) OMIM# 616,261 NM_019042.3 and splice acceptor variants in Alpha-Aminoadipic Semialdehyde Synthase; (AASS) OMIM# 605,113 NM_005763.3 was funded. Whole exome sequencing (WES) technique was used as tool to identify the molecular diagnostic test. Different bioinformatics analysis done for WES data and we identified two novel mutations one as frameshift mutation c.606_607delGA, p.Ser282CysfsTer9 in the PUS7 gene and splice acceptor variants c.1767–1 G > A in the AASS gene has been reported. The pattern of family segregation maintained the pathogenicity of this variation associated with abnormal behavior, intellectual developmental disorder, microcephaly along with short stature IDDABS. Further, the WES data was validated in the family having other affected individuals and healthy controls (n = 100) was done using Sanger sequencing. Finally, our results further explained the role of WES in the disease diagnosis and elucidated that the mutation in PUS7 and AASS genes may lead an important role for the development of IDDABS in Saudi family.
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spelling pubmed-75691392020-10-22 Next generation sequencing reveals novel homozygous frameshift in PUS7 and splice acceptor variants in AASS gene leading to intellectual disability, developmental delay, dysmorphic feature and microcephaly Naseer, Muhammad Imran Abdulkareem, Angham Abdulrahman Jan, Mohammed M. Chaudhary, Adeel G. Alharazy, Shatha AlQahtani, Mohammad H. Saudi J Biol Sci Original Article Intellectual developmental disorder with abnormal behavior, microcephaly and short stature (IDDABS), (OMIM# 618342) is an autosomal recessive condition described as developmental delay, poor or absent speech, intellectual disability, short stature, mild to progressive microcephaly, delayed psychomotor development, hyperactivity, seizure, along with mild to swear aggressive behavior. Homozygous frameshift mutation in Pseudouridine Synthase 7, Putative; (PUS7) OMIM# 616,261 NM_019042.3 and splice acceptor variants in Alpha-Aminoadipic Semialdehyde Synthase; (AASS) OMIM# 605,113 NM_005763.3 was funded. Whole exome sequencing (WES) technique was used as tool to identify the molecular diagnostic test. Different bioinformatics analysis done for WES data and we identified two novel mutations one as frameshift mutation c.606_607delGA, p.Ser282CysfsTer9 in the PUS7 gene and splice acceptor variants c.1767–1 G > A in the AASS gene has been reported. The pattern of family segregation maintained the pathogenicity of this variation associated with abnormal behavior, intellectual developmental disorder, microcephaly along with short stature IDDABS. Further, the WES data was validated in the family having other affected individuals and healthy controls (n = 100) was done using Sanger sequencing. Finally, our results further explained the role of WES in the disease diagnosis and elucidated that the mutation in PUS7 and AASS genes may lead an important role for the development of IDDABS in Saudi family. Elsevier 2020-11 2020-09-23 /pmc/articles/PMC7569139/ /pubmed/33100873 http://dx.doi.org/10.1016/j.sjbs.2020.09.033 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Naseer, Muhammad Imran
Abdulkareem, Angham Abdulrahman
Jan, Mohammed M.
Chaudhary, Adeel G.
Alharazy, Shatha
AlQahtani, Mohammad H.
Next generation sequencing reveals novel homozygous frameshift in PUS7 and splice acceptor variants in AASS gene leading to intellectual disability, developmental delay, dysmorphic feature and microcephaly
title Next generation sequencing reveals novel homozygous frameshift in PUS7 and splice acceptor variants in AASS gene leading to intellectual disability, developmental delay, dysmorphic feature and microcephaly
title_full Next generation sequencing reveals novel homozygous frameshift in PUS7 and splice acceptor variants in AASS gene leading to intellectual disability, developmental delay, dysmorphic feature and microcephaly
title_fullStr Next generation sequencing reveals novel homozygous frameshift in PUS7 and splice acceptor variants in AASS gene leading to intellectual disability, developmental delay, dysmorphic feature and microcephaly
title_full_unstemmed Next generation sequencing reveals novel homozygous frameshift in PUS7 and splice acceptor variants in AASS gene leading to intellectual disability, developmental delay, dysmorphic feature and microcephaly
title_short Next generation sequencing reveals novel homozygous frameshift in PUS7 and splice acceptor variants in AASS gene leading to intellectual disability, developmental delay, dysmorphic feature and microcephaly
title_sort next generation sequencing reveals novel homozygous frameshift in pus7 and splice acceptor variants in aass gene leading to intellectual disability, developmental delay, dysmorphic feature and microcephaly
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569139/
https://www.ncbi.nlm.nih.gov/pubmed/33100873
http://dx.doi.org/10.1016/j.sjbs.2020.09.033
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