Novel homozygous pathogenic mitochondrial DNAJC19 variant in a patient with dilated cardiomyopathy and global developmental delay
Abstract Background Dilated cardiomyopathy with ataxia syndrome (DCMA) or 3‐methylglutaconic aciduria type V is a rare global autosomal recessive mitochondrial syndrome that is clinically and genetically heterogeneous. It is characterized by early‐onset dilated cardiomyopathy and increased urinary e...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-08-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.1969 |
| _version_ | 1811219430928023552 |
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| author | Abeer Al Tuwaijri Yusra Alyafee Mashael Alharbi Maryam Ballow Mohammed Aldrees Qamre Alam Rola A. Sleiman Muhammad Umair Majid Alfadhel |
| author_facet | Abeer Al Tuwaijri Yusra Alyafee Mashael Alharbi Maryam Ballow Mohammed Aldrees Qamre Alam Rola A. Sleiman Muhammad Umair Majid Alfadhel |
| author_sort | Abeer Al Tuwaijri |
| collection | DOAJ |
| description | Abstract Background Dilated cardiomyopathy with ataxia syndrome (DCMA) or 3‐methylglutaconic aciduria type V is a rare global autosomal recessive mitochondrial syndrome that is clinically and genetically heterogeneous. It is characterized by early‐onset dilated cardiomyopathy and increased urinary excretion of 3‐methylglutaconic acid. As a result, some patients die due to cardiac failure, while others manifest with growth retardation, microcytic anemia, mild ataxia, and mild muscle weakness. DCMA is caused by variants in the DnaJ heat shock protein family (Hsp40) member C19 gene (DNAJC19), which plays an important role in mitochondrial protein import machinery in the inner mitochondrial membrane. Methods We describe a single affected family member who presented with cardiomyopathy, global developmental delay, chest infection, seizures, elevated excretion of 3‐methylglutaconic acid, and 3‐methylglutaric acid in the urine. Results Whole‐exome sequencing followed by Sanger sequencing revealed a homozygous frameshift variant in the reading frame starting at codon 54 in exon 4 in the DNAJC19 gene (c.159del [Phe54Leufs*5]), which results in a stop codon four positions downstream. Quantitative gene expression analysis revealed that DNAJC19 mRNA expression in this patient was substantially reduced compared to the control. Conclusions We present a novel variant in the DNAJC19 gene that causes rare autosomal recessive mitochondrial 3‐methylglutaconic aciduria type V. By comparing the current case with previously reported ones, we conclude that the disease is extremely heterogeneous for reasons that are still unknown. |
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| id | doaj.art-24ff3b1c93b5491089cb4bf443c751b5 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-12T07:25:38Z |
| publishDate | 2022-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-24ff3b1c93b5491089cb4bf443c751b52022-12-22T03:42:11ZengWileyMolecular Genetics & Genomic Medicine2324-92692022-08-01108n/an/a10.1002/mgg3.1969Novel homozygous pathogenic mitochondrial DNAJC19 variant in a patient with dilated cardiomyopathy and global developmental delayAbeer Al Tuwaijri0Yusra Alyafee1Mashael Alharbi2Maryam Ballow3Mohammed Aldrees4Qamre Alam5Rola A. Sleiman6Muhammad Umair7Majid Alfadhel8Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, King AbdulAziz Medical City Ministry of National Guard Health Affairs Riyadh Kingdom of Saudi ArabiaMedical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, King AbdulAziz Medical City Ministry of National Guard Health Affairs Riyadh Kingdom of Saudi ArabiaMedical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, King AbdulAziz Medical City Ministry of National Guard Health Affairs Riyadh Kingdom of Saudi ArabiaMedical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, King AbdulAziz Medical City Ministry of National Guard Health Affairs Riyadh Kingdom of Saudi ArabiaMedical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, King AbdulAziz Medical City Ministry of National Guard Health Affairs Riyadh Kingdom of Saudi ArabiaMedical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, King AbdulAziz Medical City Ministry of National Guard Health Affairs Riyadh Kingdom of Saudi ArabiaDr. Sulaiman Al‐Habib Group Al‐Rayan Hospital Riyadh Saudi ArabiaMedical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, King AbdulAziz Medical City Ministry of National Guard Health Affairs Riyadh Kingdom of Saudi ArabiaMedical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, King AbdulAziz Medical City Ministry of National Guard Health Affairs Riyadh Kingdom of Saudi ArabiaAbstract Background Dilated cardiomyopathy with ataxia syndrome (DCMA) or 3‐methylglutaconic aciduria type V is a rare global autosomal recessive mitochondrial syndrome that is clinically and genetically heterogeneous. It is characterized by early‐onset dilated cardiomyopathy and increased urinary excretion of 3‐methylglutaconic acid. As a result, some patients die due to cardiac failure, while others manifest with growth retardation, microcytic anemia, mild ataxia, and mild muscle weakness. DCMA is caused by variants in the DnaJ heat shock protein family (Hsp40) member C19 gene (DNAJC19), which plays an important role in mitochondrial protein import machinery in the inner mitochondrial membrane. Methods We describe a single affected family member who presented with cardiomyopathy, global developmental delay, chest infection, seizures, elevated excretion of 3‐methylglutaconic acid, and 3‐methylglutaric acid in the urine. Results Whole‐exome sequencing followed by Sanger sequencing revealed a homozygous frameshift variant in the reading frame starting at codon 54 in exon 4 in the DNAJC19 gene (c.159del [Phe54Leufs*5]), which results in a stop codon four positions downstream. Quantitative gene expression analysis revealed that DNAJC19 mRNA expression in this patient was substantially reduced compared to the control. Conclusions We present a novel variant in the DNAJC19 gene that causes rare autosomal recessive mitochondrial 3‐methylglutaconic aciduria type V. By comparing the current case with previously reported ones, we conclude that the disease is extremely heterogeneous for reasons that are still unknown.https://doi.org/10.1002/mgg3.19693‐methylglutaconic aciduriacardiolipindilated cardiomyopathyDNAJC19global developmental delayhomozygous |
| spellingShingle | Abeer Al Tuwaijri Yusra Alyafee Mashael Alharbi Maryam Ballow Mohammed Aldrees Qamre Alam Rola A. Sleiman Muhammad Umair Majid Alfadhel Novel homozygous pathogenic mitochondrial DNAJC19 variant in a patient with dilated cardiomyopathy and global developmental delay Molecular Genetics & Genomic Medicine 3‐methylglutaconic aciduria cardiolipin dilated cardiomyopathy DNAJC19 global developmental delay homozygous |
| title | Novel homozygous pathogenic mitochondrial DNAJC19 variant in a patient with dilated cardiomyopathy and global developmental delay |
| title_full | Novel homozygous pathogenic mitochondrial DNAJC19 variant in a patient with dilated cardiomyopathy and global developmental delay |
| title_fullStr | Novel homozygous pathogenic mitochondrial DNAJC19 variant in a patient with dilated cardiomyopathy and global developmental delay |
| title_full_unstemmed | Novel homozygous pathogenic mitochondrial DNAJC19 variant in a patient with dilated cardiomyopathy and global developmental delay |
| title_short | Novel homozygous pathogenic mitochondrial DNAJC19 variant in a patient with dilated cardiomyopathy and global developmental delay |
| title_sort | novel homozygous pathogenic mitochondrial dnajc19 variant in a patient with dilated cardiomyopathy and global developmental delay |
| topic | 3‐methylglutaconic aciduria cardiolipin dilated cardiomyopathy DNAJC19 global developmental delay homozygous |
| url | https://doi.org/10.1002/mgg3.1969 |
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