PRENATAL GENETIC TESTING FOR MULTIPLE MITOCHONDRIAL DYSFUNCTION SYNDROME CAUSED BY IBA57 GENE MUTATION KAZAKHSTANI FAMILY: A CASE REPORT

A. Gabdulkayum; Z.  Mirmanova; Т. Kadenova; М. Bayanova; L. Nazarova; А. Bolatov; A. Yerezhepov; A. Aitkulova; A. Akilzhanova; D. Yerezhepov

doi:10.26577/bb106120265

Authors

A. Gabdulkayum PI “National Laboratory Astana”, Astana, Kazakhstan https://orcid.org/0000-0003-1551-3637
Z. Mirmanova PI “National Laboratory Astana”, Astana, Kazakhstan https://orcid.org/0000-0002-0284-3891
Т. Kadenova PI “National Laboratory Astana”, Astana, Kazakhstan https://orcid.org/0009-0007-7104-1415
М. Bayanova Corporate Found “University Medical Center”, Astana, Kazakhstan https://orcid.org/0000-0002-6167-5357
L. Nazarova Corporate Found “University Medical Center”, Astana, Kazakhstan https://orcid.org/0000-0002-3325-5240
А. Bolatov Corporate Found “University Medical Center”, Astana, Kazakhstan https://orcid.org/0000-0002-5390-4623
A. Yerezhepov Al-Farabi Kazakh National University, Almaty, Kazakhstan https://orcid.org/0009-0009-6968-6948
A. Aitkulova PI “National Laboratory Astana”, Astana, Kazakhstan https://orcid.org/0000-0001-5016-0932
A. Akilzhanova PI “National Laboratory Astana”, Astana, Kazakhstan https://orcid.org/0000-0001-6161-8355
D. Yerezhepov PI “National Laboratory Astana”, Astana, Kazakhstan https://orcid.org/0000-0002-4161-1348

DOI:

https://doi.org/10.26577/bb106120265

Keywords:

синдром множественной митохондриальной дисфункции 3; пренатальное генетическое тестирование; IBA57; генетическое консультирование; информированное репродуктивное решение.

Abstract

Mitochondria, commonly known as the cell’s power generator, carry out their primary function through oxidative phosphorylation (OXPHOS), a process that produces ATP, the main energy source of the cell and the only cell organelles with their own mitochondrial DNA. Any genetic alterations in DNA sequences that encode mitochondrial structural or functional proteins may cause mitochondrial disorders. Multiple mitochondrial dysfunction syndrome type 3 (MMDS3) is a rare autosomal recessive mitochondrial disorder caused by homozygous or biallelic pathogenic variants in the IBA57 gene. In the current study, we present a case report on prenatal genetic testing for multiple mitochondrial dysfunction syndrome (MMDS) type 3 caused by the IBA57 gene to highlight the importance of prenatal diagnostics for disease prognosis and treatment, appropriate genetic counselling, and informed reproductive decision-making. We recruited a 27-year-old G2P1001 at 22 weeks’ gestation with MMDS3 in family history, confirmed by whole exome sequencing (WES) and also verified by Sanger sequencing in the IBA57 gene c.286T>C (NM_001010867.4, p.Tyr96His) and c.667C>G (NM_001010867.4, p.Arg223Gly) in the proband and parents. The ccfDNA genetic test revealed the absence of the heterozygous IBA57 gene variant at position c.286T>C (NM_001010867.4, p.Tyr96His), but the heterozygous IBA57 gene variant at position c.667C>G (NM_001010867.4, p.Arg223Gly) was detected. The child is a heterozygous carrier of the genetic variant of the IBA57 gene at position c.667C>G (NM_001010867.4, p.Arg223Gly). No specific treatment is required; observation by a pediatrician and medical and genetic counseling of the couple when planning the next pregnancy are recommended. The IBA57 gene-related MMDS3 can have a wide range of outcomes and consequences and may progress rapidly. Early awareness is crucial to prompt and proper administration. Our study reveals the importance of early prenatal genetic testing for IBA57-related MMDS3 for early diagnostics and consent decision-making.

Author Biographies

A. Gabdulkayum, PI “National Laboratory Astana”, Astana, Kazakhstan

Aidana Gabdulkayum - Junior Researcher, Laboratory of Genomic and Personalized Medicine, PI “National Laboratory Astana”, Astana, Kazakhstan. Postal address: Kazakhstan, Z05H0P9, Astana, Kabanbay Batyr Ave. 53. E-mail: gabdulkayum@nu.edu.kz.

Z. Mirmanova, PI “National Laboratory Astana”, Astana, Kazakhstan

Zhanel Mirmanova – Research Assistant, Laboratory of Genomic and Personalized Medicine, PI “National Laboratory Astana”, Astana, Kazakhstan. Postal address: 53, Kabanbay Batyr Ave., Z05H0P9, Astana, Kazakhstan. E-mail: mirmanova@nu.edu.kz.

Т. Kadenova, PI “National Laboratory Astana”, Astana, Kazakhstan

Tomiris Kadenova – Research Assistant, Laboratory of Genomic and Personalized Medicine, PI “National Laboratory Astana”, Astana, Kazakhstan. Postal address: 53, Kabanbay Batyr Ave., Z05H0P9, Astana, Kazakhstan. E-mail: kadenova@nu.edu.kz.

М. Bayanova, Corporate Found “University Medical Center”, Astana, Kazakhstan

Mirgul Bayanova, Head of the Genetic Unit, Department of Laboratory Medicine, Pathology and Genetics, Corporate Found “University Medical Center”, Astana, Republic of Kazakhstan. Postal address: 44, Turan Ave., 010000, Astana, Kazakhstan. E-mail: Bayanova@umc.org.kz.

L. Nazarova, Corporate Found “University Medical Center”, Astana, Kazakhstan

Lyazzat Nazarova, MD, Clinical cytogeneticist, Corporate Found “University Medical Center”, Astana, Republic of Kazakhstan. Postal address: 44, Turan Ave., 010000, Astana, Kazakhstan. E-mail: nazarova@umc.org.kz.

А. Bolatov, Corporate Found “University Medical Center”, Astana, Kazakhstan

Aidos Bolatov, Researcher, Department of Clinical and Genetic Diagnostics, Corporate Found “University Medical Center”, Astana, Kazakhstan. Postal address: 44, Turan Ave., 010000, Astana, Kazakhstan. E-mail: bolatovaidos@gmail.com.

A. Yerezhepov, Al-Farabi Kazakh National University, Almaty, Kazakhstan

Adil Yerezhepov, Candidate of Biological Sciences, Associate Professor, Department of Biology and Biotechnology, NJSC “Al-Farabi Kazakh National University”, Almaty, Kazakhstan. Postal address: 93, Al Farabi Ave., 020000, Almaty, Kazakhstan. Email: yerezhepov@mail.ru.

A. Aitkulova, PI “National Laboratory Astana”, Astana, Kazakhstan

Akbota Aikulova – PhD, Senior Researcher, Laboratory of Genomic and Personalized Medicine, PI “National Laboratory Astana”, Astana, Kazakhstan. Postal address: 53, Kabanbay Batyr Ave., Z05H0P9, Astana, Kazakhstan. E-mail: aitkulova@nu.edu.kz.

A. Akilzhanova, PI “National Laboratory Astana”, Astana, Kazakhstan

Ainur Akilzhanova – Doctor of Medical Sciences, PhD, M.D., Professor, Head of Laboratory of Genomic and Personalized Medicine, PI “National Laboratory Astana”, Astana, Kazakhstan. Postal address: 53, Kabanbay Batyr Ave., Z05H0P9, Astana, Kazakhstan. E-mail: akilzhanova@nu.edu.kz.

D. Yerezhepov, PI “National Laboratory Astana”, Astana, Kazakhstan

Dauren Yerezhepov (corresponding author) – PhD, Leading Researcher, Laboratory of Genomic and Personalized Medicine, PI “National Laboratory Astana”, Astana, Kazakhstan. Postal address: 53, Kabanbay Batyr Ave., Z05H0P9, Astana, Kazakhstan. E-mail: yerezhepov@nu.edu.kz.