Multiple Mitochondrial Dysfunction Syndrome Type 3: A Likely Pathogenic Homozygous Variant Affecting a Patient of Cuban Descent and Literature Review

Lang, Steven H.; Camponeschi, Francesca; de Joya, Evan; Borjas-Mendoza, Paulo; Tekin, Mustafa; Thorson, Willa

doi:10.3390/genes13112044

Open AccessArticle

Multiple Mitochondrial Dysfunction Syndrome Type 3: A Likely Pathogenic Homozygous Variant Affecting a Patient of Cuban Descent and Literature Review

by

Steven H. Lang

¹

,

Francesca Camponeschi

²

,

Evan de Joya

¹

,

Paulo Borjas-Mendoza

¹,

Mustafa Tekin

¹ and

Willa Thorson

^1,*

¹

Dr. John T. Macdonald Foundation, Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA

²

Magnetic Resonance Center, University of Florence, 50019 Florence, Italy

^*

Author to whom correspondence should be addressed.

Genes 2022, 13(11), 2044; https://doi.org/10.3390/genes13112044

Submission received: 10 September 2022 / Revised: 31 October 2022 / Accepted: 4 November 2022 / Published: 6 November 2022

(This article belongs to the Section Human Genomics and Genetic Diseases)

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Abstract

Multiple mitochondrial dysfunction syndrome type 3 (MMDS3) is a rare mitochondrial leukoencephalopathy caused by biallelic pathogenic variants in IBA57. Here, we describe a homozygous variant in IBA57, (NM_001010867.2): c.310G>T (p.Gly104Cys), in a 2-month-old infant of Cuban descent who presented with a one-month history of progressive hypotonia, weakness, and episodes of upgaze deviation. This is the first report of a patient homozygous for this variant and the first report of MMDS3 in a patient of Hispanic descent described to our knowledge. Using in silico tools, we found that the variant resides in a putative mutational hotspot located in the neighborhood of a key active ligand required for iron-sulfur cluster coordination. In addition, while previous case reports/series have reported the variable phenotypic features of the disease, the incidence of these features across the literature has not been well described. In order to construct a clearer global picture of the typical presentation of MMDS3, we reviewed 52 cases across the literature with respect to their clinical, biochemical, genotypic, and neuroradiographic features.

Keywords: multiple mitochondrial dysfunction syndrome; MMDS; IBA57; iron-sulfur clusters; leukoencephalopathy

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MDPI and ACS Style

Lang, S.H.; Camponeschi, F.; de Joya, E.; Borjas-Mendoza, P.; Tekin, M.; Thorson, W. Multiple Mitochondrial Dysfunction Syndrome Type 3: A Likely Pathogenic Homozygous Variant Affecting a Patient of Cuban Descent and Literature Review. Genes 2022, 13, 2044. https://doi.org/10.3390/genes13112044

AMA Style

Lang SH, Camponeschi F, de Joya E, Borjas-Mendoza P, Tekin M, Thorson W. Multiple Mitochondrial Dysfunction Syndrome Type 3: A Likely Pathogenic Homozygous Variant Affecting a Patient of Cuban Descent and Literature Review. Genes. 2022; 13(11):2044. https://doi.org/10.3390/genes13112044

Chicago/Turabian Style

Lang, Steven H., Francesca Camponeschi, Evan de Joya, Paulo Borjas-Mendoza, Mustafa Tekin, and Willa Thorson. 2022. "Multiple Mitochondrial Dysfunction Syndrome Type 3: A Likely Pathogenic Homozygous Variant Affecting a Patient of Cuban Descent and Literature Review" Genes 13, no. 11: 2044. https://doi.org/10.3390/genes13112044

APA Style

Lang, S. H., Camponeschi, F., de Joya, E., Borjas-Mendoza, P., Tekin, M., & Thorson, W. (2022). Multiple Mitochondrial Dysfunction Syndrome Type 3: A Likely Pathogenic Homozygous Variant Affecting a Patient of Cuban Descent and Literature Review. Genes, 13(11), 2044. https://doi.org/10.3390/genes13112044

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Multiple Mitochondrial Dysfunction Syndrome Type 3: A Likely Pathogenic Homozygous Variant Affecting a Patient of Cuban Descent and Literature Review

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