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Live Birth of a Healthy Child in a Couple with Identical mtDNA Carrying a Pathogenic c.471_477delTTTAAAAinsG Variant in the MOCS2 Gene

Molybdenum cofactor deficiency type B (MOCODB; #252160) is an autosomal recessive metabolic disorder that has only been described in 37 affected patients. In this report, we describe the presence of an in-frame homozygous variant (c.471_477delTTTAAAAinsG) in the MOCS2 gene in an affected child, diag...

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Autores principales: Tofilo, Maria, Voronova, Natalia, Nigmatullina, Leila, Kuznetsova, Elena, Timonina, Valeria, Efimenko, Bogdan, Turgunkhujaev, Oybek, Avdeichik, Svetlana, Ansar, Muhammad, Popadin, Konstantin, Kirillova, Anastasia, Mazunin, Ilya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10048300/
https://www.ncbi.nlm.nih.gov/pubmed/36980992
http://dx.doi.org/10.3390/genes14030720
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author Tofilo, Maria
Voronova, Natalia
Nigmatullina, Leila
Kuznetsova, Elena
Timonina, Valeria
Efimenko, Bogdan
Turgunkhujaev, Oybek
Avdeichik, Svetlana
Ansar, Muhammad
Popadin, Konstantin
Kirillova, Anastasia
Mazunin, Ilya
author_facet Tofilo, Maria
Voronova, Natalia
Nigmatullina, Leila
Kuznetsova, Elena
Timonina, Valeria
Efimenko, Bogdan
Turgunkhujaev, Oybek
Avdeichik, Svetlana
Ansar, Muhammad
Popadin, Konstantin
Kirillova, Anastasia
Mazunin, Ilya
author_sort Tofilo, Maria
collection PubMed
description Molybdenum cofactor deficiency type B (MOCODB; #252160) is an autosomal recessive metabolic disorder that has only been described in 37 affected patients. In this report, we describe the presence of an in-frame homozygous variant (c.471_477delTTTAAAAinsG) in the MOCS2 gene in an affected child, diagnosed with Ohtahara syndrome according to the clinical manifestations. The analysis of the three-dimensional structure of the protein and the amino acid substitutions suggested the pathogenicity of this mutation. To prevent transmitting this mutation to the next generation, we used preimplantation genetic testing for the monogenic disorders (PGT-M) protocol to select MOCS2 gene mutant-free embryos for transfer in an in vitro fertilization (IVF) program. As a result, a healthy child was born. Interestingly, both parents of the proband shared an identical mitochondrial (mt) DNA control region, assuming their close relationship and thus suggesting that both copies of the nuclear rare variant c.471_477delTTTAAAAinsG may have been transmitted from the same female ancestor. Our estimation of the a priori probability of meeting individuals with the same mtDNA haplotype confirms the assumption of a possible distant maternal relationship among the proband’s direct relatives.
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spelling pubmed-100483002023-03-29 Live Birth of a Healthy Child in a Couple with Identical mtDNA Carrying a Pathogenic c.471_477delTTTAAAAinsG Variant in the MOCS2 Gene Tofilo, Maria Voronova, Natalia Nigmatullina, Leila Kuznetsova, Elena Timonina, Valeria Efimenko, Bogdan Turgunkhujaev, Oybek Avdeichik, Svetlana Ansar, Muhammad Popadin, Konstantin Kirillova, Anastasia Mazunin, Ilya Genes (Basel) Case Report Molybdenum cofactor deficiency type B (MOCODB; #252160) is an autosomal recessive metabolic disorder that has only been described in 37 affected patients. In this report, we describe the presence of an in-frame homozygous variant (c.471_477delTTTAAAAinsG) in the MOCS2 gene in an affected child, diagnosed with Ohtahara syndrome according to the clinical manifestations. The analysis of the three-dimensional structure of the protein and the amino acid substitutions suggested the pathogenicity of this mutation. To prevent transmitting this mutation to the next generation, we used preimplantation genetic testing for the monogenic disorders (PGT-M) protocol to select MOCS2 gene mutant-free embryos for transfer in an in vitro fertilization (IVF) program. As a result, a healthy child was born. Interestingly, both parents of the proband shared an identical mitochondrial (mt) DNA control region, assuming their close relationship and thus suggesting that both copies of the nuclear rare variant c.471_477delTTTAAAAinsG may have been transmitted from the same female ancestor. Our estimation of the a priori probability of meeting individuals with the same mtDNA haplotype confirms the assumption of a possible distant maternal relationship among the proband’s direct relatives. MDPI 2023-03-15 /pmc/articles/PMC10048300/ /pubmed/36980992 http://dx.doi.org/10.3390/genes14030720 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
Tofilo, Maria
Voronova, Natalia
Nigmatullina, Leila
Kuznetsova, Elena
Timonina, Valeria
Efimenko, Bogdan
Turgunkhujaev, Oybek
Avdeichik, Svetlana
Ansar, Muhammad
Popadin, Konstantin
Kirillova, Anastasia
Mazunin, Ilya
Live Birth of a Healthy Child in a Couple with Identical mtDNA Carrying a Pathogenic c.471_477delTTTAAAAinsG Variant in the MOCS2 Gene
title Live Birth of a Healthy Child in a Couple with Identical mtDNA Carrying a Pathogenic c.471_477delTTTAAAAinsG Variant in the MOCS2 Gene
title_full Live Birth of a Healthy Child in a Couple with Identical mtDNA Carrying a Pathogenic c.471_477delTTTAAAAinsG Variant in the MOCS2 Gene
title_fullStr Live Birth of a Healthy Child in a Couple with Identical mtDNA Carrying a Pathogenic c.471_477delTTTAAAAinsG Variant in the MOCS2 Gene
title_full_unstemmed Live Birth of a Healthy Child in a Couple with Identical mtDNA Carrying a Pathogenic c.471_477delTTTAAAAinsG Variant in the MOCS2 Gene
title_short Live Birth of a Healthy Child in a Couple with Identical mtDNA Carrying a Pathogenic c.471_477delTTTAAAAinsG Variant in the MOCS2 Gene
title_sort live birth of a healthy child in a couple with identical mtdna carrying a pathogenic c.471_477deltttaaaainsg variant in the mocs2 gene
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10048300/
https://www.ncbi.nlm.nih.gov/pubmed/36980992
http://dx.doi.org/10.3390/genes14030720
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