Multiple Mitochondrial Dysfunction Syndrome Type 3: A Likely Pathogenic Homozygous Variant Affecting a Patient of Cuban Descent and Literature Review
Multiple mitochondrial dysfunction syndrome type 3 (MMDS3) is a rare mitochondrial leukoencephalopathy caused by biallelic pathogenic variants in <i>IBA57</i>. Here, we describe a homozygous variant in <i>IBA57</i>, (NM_001010867.2): c.310G>T (p.Gly104Cys), in a 2-month-ol...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/11/2044 |
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| author | Steven H. Lang Francesca Camponeschi Evan de Joya Paulo Borjas-Mendoza Mustafa Tekin Willa Thorson |
| author_facet | Steven H. Lang Francesca Camponeschi Evan de Joya Paulo Borjas-Mendoza Mustafa Tekin Willa Thorson |
| author_sort | Steven H. Lang |
| collection | DOAJ |
| description | Multiple mitochondrial dysfunction syndrome type 3 (MMDS3) is a rare mitochondrial leukoencephalopathy caused by biallelic pathogenic variants in <i>IBA57</i>. Here, we describe a homozygous variant in <i>IBA57</i>, (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. |
| first_indexed | 2024-03-09T19:03:18Z |
| format | Article |
| id | doaj.art-33ed45f81a6d4dfaa8749bc1182b1ab9 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T19:03:18Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-33ed45f81a6d4dfaa8749bc1182b1ab92023-11-24T04:48:54ZengMDPI AGGenes2073-44252022-11-011311204410.3390/genes13112044Multiple Mitochondrial Dysfunction Syndrome Type 3: A Likely Pathogenic Homozygous Variant Affecting a Patient of Cuban Descent and Literature ReviewSteven H. Lang0Francesca Camponeschi1Evan de Joya2Paulo Borjas-Mendoza3Mustafa Tekin4Willa Thorson5Dr. John T. Macdonald Foundation, Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL 33136, USAMagnetic Resonance Center, University of Florence, 50019 Florence, ItalyDr. John T. Macdonald Foundation, Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL 33136, USADr. John T. Macdonald Foundation, Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL 33136, USADr. John T. Macdonald Foundation, Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL 33136, USADr. John T. Macdonald Foundation, Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL 33136, USAMultiple mitochondrial dysfunction syndrome type 3 (MMDS3) is a rare mitochondrial leukoencephalopathy caused by biallelic pathogenic variants in <i>IBA57</i>. Here, we describe a homozygous variant in <i>IBA57</i>, (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.https://www.mdpi.com/2073-4425/13/11/2044multiple mitochondrial dysfunction syndromeMMDSIBA57iron-sulfur clustersleukoencephalopathy |
| spellingShingle | Steven H. Lang Francesca Camponeschi Evan de Joya Paulo Borjas-Mendoza Mustafa Tekin Willa Thorson Multiple Mitochondrial Dysfunction Syndrome Type 3: A Likely Pathogenic Homozygous Variant Affecting a Patient of Cuban Descent and Literature Review Genes multiple mitochondrial dysfunction syndrome MMDS IBA57 iron-sulfur clusters leukoencephalopathy |
| title | Multiple Mitochondrial Dysfunction Syndrome Type 3: A Likely Pathogenic Homozygous Variant Affecting a Patient of Cuban Descent and Literature Review |
| title_full | Multiple Mitochondrial Dysfunction Syndrome Type 3: A Likely Pathogenic Homozygous Variant Affecting a Patient of Cuban Descent and Literature Review |
| title_fullStr | Multiple Mitochondrial Dysfunction Syndrome Type 3: A Likely Pathogenic Homozygous Variant Affecting a Patient of Cuban Descent and Literature Review |
| title_full_unstemmed | Multiple Mitochondrial Dysfunction Syndrome Type 3: A Likely Pathogenic Homozygous Variant Affecting a Patient of Cuban Descent and Literature Review |
| title_short | Multiple Mitochondrial Dysfunction Syndrome Type 3: A Likely Pathogenic Homozygous Variant Affecting a Patient of Cuban Descent and Literature Review |
| title_sort | multiple mitochondrial dysfunction syndrome type 3 a likely pathogenic homozygous variant affecting a patient of cuban descent and literature review |
| topic | multiple mitochondrial dysfunction syndrome MMDS IBA57 iron-sulfur clusters leukoencephalopathy |
| url | https://www.mdpi.com/2073-4425/13/11/2044 |
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