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 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 presente...
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Veröffentlicht in: | Genes 2022-11, Vol.13 (11), p.2044 |
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description | 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. |
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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.</description><identifier>ISSN: 2073-4425</identifier><identifier>EISSN: 2073-4425</identifier><identifier>DOI: 10.3390/genes13112044</identifier><identifier>PMID: 36360281</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Case reports ; Dehydrogenases ; Genetic aspects ; Genetic variation ; Genomes ; Genomics ; Genotype & phenotype ; Health aspects ; Leukoencephalopathy ; Literature reviews ; Missing data ; Mitochondria ; Mitochondrial diseases ; Mitochondrial DNA ; Patients ; Sulfur</subject><ispartof>Genes, 2022-11, Vol.13 (11), p.2044</ispartof><rights>COPYRIGHT 2022 MDPI AG</rights><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. 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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.</description><subject>Case reports</subject><subject>Dehydrogenases</subject><subject>Genetic aspects</subject><subject>Genetic variation</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Genotype & phenotype</subject><subject>Health aspects</subject><subject>Leukoencephalopathy</subject><subject>Literature reviews</subject><subject>Missing data</subject><subject>Mitochondria</subject><subject>Mitochondrial diseases</subject><subject>Mitochondrial DNA</subject><subject>Patients</subject><subject>Sulfur</subject><issn>2073-4425</issn><issn>2073-4425</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNptkk1v1DAQhiMEolXpkbslLlzSOv6IYw5Iqy20SFuBoHC1HGe865LYi50Uhf_B_8VRK2AR9sGj18-8nrGmKJ5X-IxSic-34CFVtKoIZuxRcUywoCVjhD_-Kz4qTlO6xXkxTDDmT4sjWtMak6Y6Ln5eT_3o9j2gazcGswu-i0736GJOdvJmdMGjT3MWwwDoZt4Doq_QCm3cV-hn9EGPu5CLcAZdhSH8mLdhSuiLzhZ-RCtrITv4LdIL6SBrwaL11GqPLiCZRdC-y24jRD1OEdBHuHPw_VnxxOo-wenDeVJ8fvvmZn1Vbt5fvluvNqVhXI5lTRojGiKkpV2rCW66hhpMaCtaoknLSQ2Y113DaCu1xlTXwKFjBhvLKBWSnhSv7333UztAtxQUda_20Q06zipopw5vvNupbbhTspa45jQbvHwwiOHbBGlUg8t99b32kL9CEUF5IzihC_riH_Q2TNHn9jLFGiJJLcQfaqt7UM7bkN81i6laCcZFJaXgmTr7D5V3B4MzwYN1WT9IKO8TTAwpRbC_e6ywWkZJHYwS_QU6Nbul</recordid><startdate>20221106</startdate><enddate>20221106</enddate><creator>Lang, Steven H</creator><creator>Camponeschi, Francesca</creator><creator>de Joya, Evan</creator><creator>Borjas-Mendoza, Paulo</creator><creator>Tekin, Mustafa</creator><creator>Thorson, Willa</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4369-7082</orcidid><orcidid>https://orcid.org/0000-0002-5259-1039</orcidid><orcidid>https://orcid.org/0000-0002-4122-4508</orcidid></search><sort><creationdate>20221106</creationdate><title>Multiple Mitochondrial Dysfunction Syndrome Type 3: A Likely Pathogenic Homozygous Variant Affecting a Patient of Cuban Descent and Literature Review</title><author>Lang, Steven H ; 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subjects | Case reports Dehydrogenases Genetic aspects Genetic variation Genomes Genomics Genotype & phenotype Health aspects Leukoencephalopathy Literature reviews Missing data Mitochondria Mitochondrial diseases Mitochondrial DNA Patients Sulfur |
title | Multiple Mitochondrial Dysfunction Syndrome Type 3: A Likely Pathogenic Homozygous Variant Affecting a Patient of Cuban Descent and Literature Review |
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