Identification of a putative founder variant in SLC30A10 associated with hypermanganesemia with dystonia 1 in Iranian patients: a case series and literature review.
11 affiliations
- 1Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
- 2Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- 3Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
- 4Center for Individualized Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
- 5Department of Pharmacology-Physiology, Université de Sherbrooke - Campus de la santé, Sherbrooke, Québec, Canada.
- 6Genetic Center of Khorasan Razavi, Mashhad, Iran.
- 7Department of Biochemistry, Mashhad University of Ferdowsi, Mashhad, Iran.
- 8Rare Pediatric Neurological Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- 9Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. [email protected].
- 10Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. [email protected].
- 11Genetic Center of Khorasan Razavi, Mashhad, Iran. [email protected].
Abstract
Hypermanganesemia with dystonia 1 (HMNDYT1) is an rare autosomal recessive condition resulting from pathogenic variants in the SLC30A10 gene. The presence of biallelic variants in this gene results in systemic accumulation of manganese, which leads to dystonia, polycythemia, and liver dysfunction. We conducted clinical and genetic evaluations of seven affected individuals from six Iranian consanguineous families, emphasizing the identification of potential founder mutations, and integrated this information with a total of 80 previously reported cases. Analysis of exome sequencing in all seven individuals affected revealed the presence of the identical homozygous variant in SLC30A10 (c.1006 C > T; p.His336Tyr), suggesting a potential founder effect. The estimated most recent common ancestor for these patients lived approximately 47 generations ago, suggesting an ancient mutation originating from a common ancestor. A literature review of 80 reported HMNDYT1 cases demonstrated that hypermanganesemia, T1 hyperintensity of the basal ganglia and dentate nuclei, dystonia, and polycythemia constitute the predominant clinical features. Symptom onset occurred primarily within the first five years of life (median: ~2 years, range: 0.25-57 years). Collectively, these observations underscore the need to identify potential founder variants and to more comprehensively characterize the genotypic and phenotypic spectrum of SLC30A10 to inform genetic counseling and population-based screening strategies.
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BibTeX
@article{eslahi2026identification,
title = {{Identification of a putative founder variant in SLC30A10 associated with hypermanganesemia with dystonia 1 in Iranian patients: a case series and literature review.}},
author = {Atieh Eslahi and Farzaneh Alizadeh and Arash Salmaninejad and Sadaf Ghanaatgar-Kasbi and Karim Naghipour Kojur and Mir Salar Kahaei and Leila Hamzehzadeh and Masoome Alerasool and Mahsa Sadat Asl Mohajeri and Azam Rastegar Moghaddam and Shima Farrokhi and Yasamin Yousefi and Mehran Beiraghi Toosi and Majid Mojarrad},
journal = {BMC medical genomics},
year = {2026},
month = jul,
doi = {10.1186/s12920-026-02350-5},
url = {https://europepmc.org/article/MED/42902376},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Identification of a putative founder variant in SLC30A10 associated with hypermanganesemia with dystonia 1 in Iranian patients: a case series and literature review.
AU - Atieh Eslahi
AU - Farzaneh Alizadeh
AU - Arash Salmaninejad
AU - Sadaf Ghanaatgar-Kasbi
AU - Karim Naghipour Kojur
AU - Mir Salar Kahaei
AU - Leila Hamzehzadeh
AU - Masoome Alerasool
AU - Mahsa Sadat Asl Mohajeri
AU - Azam Rastegar Moghaddam
AU - Shima Farrokhi
AU - Yasamin Yousefi
AU - Mehran Beiraghi Toosi
AU - Majid Mojarrad
PY - 2026
DA - 2026/07/01
JO - BMC medical genomics
DO - 10.1186/s12920-026-02350-5
UR - https://europepmc.org/article/MED/42902376
AB - Hypermanganesemia with dystonia 1 (HMNDYT1) is an rare autosomal recessive condition resulting from pathogenic variants in the SLC30A10 gene. The presence of biallelic variants in this gene results in systemic accumulation of manganese, which leads to dystonia, polycythemia, and liver dysfunction. We conducted clinical and genetic evaluations of seven affected individuals from six Iranian consanguineous families, emphasizing the identification of potential founder mutations, and integrated this information with a total of 80 previously reported cases. Analysis of exome sequencing in all seven individuals affected revealed the presence of the identical homozygous variant in SLC30A10 (c.1006 C > T; p.His336Tyr), suggesting a potential founder effect. The estimated most recent common ancestor for these patients lived approximately 47 generations ago, suggesting an ancient mutation originating from a common ancestor. A literature review of 80 reported HMNDYT1 cases demonstrated that hypermanganesemia, T1 hyperintensity of the basal ganglia and dentate nuclei, dystonia, and polycythemia constitute the predominant clinical features. Symptom onset occurred primarily within the first five years of life (median: ~2 years, range: 0.25-57 years). Collectively, these observations underscore the need to identify potential founder variants and to more comprehensively characterize the genotypic and phenotypic spectrum of SLC30A10 to inform genetic counseling and population-based screening strategies.
SN - 1755-8794
ER -