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Microcephaly, Short Stature, Intellectual Disability, Speech Absence and Cataract Are Associated with Novel Bi-Allelic Missense Variant in RTTN Gene: A Seckel Syndrome Case Report

The RTTN gene encodes centriole biogenesis, replication, symmetry and cohesion, basal body organization and has recently been associated with the appearance of microcephaly syndromes. RTTN-related neurological defects including microcephaly, intellectual disability, congenital dwarfism, ophthalmic m...

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Autores principales: Mudassir, Behjat Ul, Agha, Zehra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10297240/
https://www.ncbi.nlm.nih.gov/pubmed/37371259
http://dx.doi.org/10.3390/children10061027
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author Mudassir, Behjat Ul
Agha, Zehra
author_facet Mudassir, Behjat Ul
Agha, Zehra
author_sort Mudassir, Behjat Ul
collection PubMed
description The RTTN gene encodes centriole biogenesis, replication, symmetry and cohesion, basal body organization and has recently been associated with the appearance of microcephaly syndromes. RTTN-related neurological defects including microcephaly, intellectual disability, congenital dwarfism, ophthalmic manifestations, and epilepsy are mainly due to abnormal brain development pathways and loss-of-function protein mutations. We present a consanguineous Pakistani family clinically suspected of Seckel syndrome with severe microcephaly, severe intellectual disability, short stature, absence of speech, pointed nose, narrow face and bilateral cataract in two siblings residing in the suburbs of Islamabad. Forty cases of Seckel syndrome have been reported to date in the literature due to mutations in the ATR, TRAIP, RBBP8, NSMCE2, NIN, CENPJ, DNA2, CEP152 and CEP63  genes. The objective of the study was to perform a clinical diagnosis, genetic analysis, and pathophysiology of Seckel syndrome in the proband. Whole-exome sequencing discovered NM_173630.4: c.57G > T(pGlu19Asp) missense variant in exon 2 of the RTTN gene that co-segregates in the family. This novel variant, to the best of our knowledge, is pathogenic and with autosomal recessive inheritance expressed as Seckel syndrome in the affected members of the family. The present study has expanded the genetic knowledge of novel RTTN gene variants associated with Seckel syndrome and has broadened its phenotype spectrum in the Pakistani population, which comprises diverse ethnicities. We hope that our study will open new horizons for individual molecular diagnosis and therapeutics to improve the life of patients with this congenital syndrome.
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spelling pubmed-102972402023-06-28 Microcephaly, Short Stature, Intellectual Disability, Speech Absence and Cataract Are Associated with Novel Bi-Allelic Missense Variant in RTTN Gene: A Seckel Syndrome Case Report Mudassir, Behjat Ul Agha, Zehra Children (Basel) Case Report The RTTN gene encodes centriole biogenesis, replication, symmetry and cohesion, basal body organization and has recently been associated with the appearance of microcephaly syndromes. RTTN-related neurological defects including microcephaly, intellectual disability, congenital dwarfism, ophthalmic manifestations, and epilepsy are mainly due to abnormal brain development pathways and loss-of-function protein mutations. We present a consanguineous Pakistani family clinically suspected of Seckel syndrome with severe microcephaly, severe intellectual disability, short stature, absence of speech, pointed nose, narrow face and bilateral cataract in two siblings residing in the suburbs of Islamabad. Forty cases of Seckel syndrome have been reported to date in the literature due to mutations in the ATR, TRAIP, RBBP8, NSMCE2, NIN, CENPJ, DNA2, CEP152 and CEP63  genes. The objective of the study was to perform a clinical diagnosis, genetic analysis, and pathophysiology of Seckel syndrome in the proband. Whole-exome sequencing discovered NM_173630.4: c.57G > T(pGlu19Asp) missense variant in exon 2 of the RTTN gene that co-segregates in the family. This novel variant, to the best of our knowledge, is pathogenic and with autosomal recessive inheritance expressed as Seckel syndrome in the affected members of the family. The present study has expanded the genetic knowledge of novel RTTN gene variants associated with Seckel syndrome and has broadened its phenotype spectrum in the Pakistani population, which comprises diverse ethnicities. We hope that our study will open new horizons for individual molecular diagnosis and therapeutics to improve the life of patients with this congenital syndrome. MDPI 2023-06-08 /pmc/articles/PMC10297240/ /pubmed/37371259 http://dx.doi.org/10.3390/children10061027 Text en © 2023 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 Case Report
Mudassir, Behjat Ul
Agha, Zehra
Microcephaly, Short Stature, Intellectual Disability, Speech Absence and Cataract Are Associated with Novel Bi-Allelic Missense Variant in RTTN Gene: A Seckel Syndrome Case Report
title Microcephaly, Short Stature, Intellectual Disability, Speech Absence and Cataract Are Associated with Novel Bi-Allelic Missense Variant in RTTN Gene: A Seckel Syndrome Case Report
title_full Microcephaly, Short Stature, Intellectual Disability, Speech Absence and Cataract Are Associated with Novel Bi-Allelic Missense Variant in RTTN Gene: A Seckel Syndrome Case Report
title_fullStr Microcephaly, Short Stature, Intellectual Disability, Speech Absence and Cataract Are Associated with Novel Bi-Allelic Missense Variant in RTTN Gene: A Seckel Syndrome Case Report
title_full_unstemmed Microcephaly, Short Stature, Intellectual Disability, Speech Absence and Cataract Are Associated with Novel Bi-Allelic Missense Variant in RTTN Gene: A Seckel Syndrome Case Report
title_short Microcephaly, Short Stature, Intellectual Disability, Speech Absence and Cataract Are Associated with Novel Bi-Allelic Missense Variant in RTTN Gene: A Seckel Syndrome Case Report
title_sort microcephaly, short stature, intellectual disability, speech absence and cataract are associated with novel bi-allelic missense variant in rttn gene: a seckel syndrome case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10297240/
https://www.ncbi.nlm.nih.gov/pubmed/37371259
http://dx.doi.org/10.3390/children10061027
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