<i>DNAJC30</i> Gene Variants Are a Frequent Cause of a Rare Disease: Leber Hereditary Optic Neuropathy in Polish Patients
Leber hereditary optic neuropathy (LHON) is a rare disorder causing a sudden painless loss of visual acuity in one or both eyes, affecting young males in their second to third decade of life. The molecular background of the LHON is up to 90%, genetically defined by a point mutation in mitochondrial...
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/24/17496 |
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| author | Anna Skorczyk-Werner Katarzyna Tońska Aleksandra Maciejczuk Katarzyna Nowomiejska Magdalena Korwin Monika Ołdak Anna Wawrocka Maciej R. Krawczyński |
| author_facet | Anna Skorczyk-Werner Katarzyna Tońska Aleksandra Maciejczuk Katarzyna Nowomiejska Magdalena Korwin Monika Ołdak Anna Wawrocka Maciej R. Krawczyński |
| author_sort | Anna Skorczyk-Werner |
| collection | DOAJ |
| description | Leber hereditary optic neuropathy (LHON) is a rare disorder causing a sudden painless loss of visual acuity in one or both eyes, affecting young males in their second to third decade of life. The molecular background of the LHON is up to 90%, genetically defined by a point mutation in mitochondrial DNA. Recently, an autosomal recessive form of LHON (LHONAR1, arLHON) has been discovered, caused by biallelic variants in the <i>DNAJC30</i> gene. This study provides the results of the <i>DNAJC30</i> gene analysis in a large group of 46 Polish patients diagnosed with LHON, together with the clinical characterization of the disease. The c.152A>G (p.Tyr51Cys) substitution in the <i>DNAJC30</i> gene was detected in all the patients as homozygote or compound heterozygote. Moreover, we identified one novel variant, c.293A>G, p.(Tyr98Cys), as well as two ultra-rare <i>DNAJC30</i> variants: c.293A>C, p.(Tyr98Ser), identified to date only in one individual affected with LHONAR1, and c.130_131delTC (p.Ser44ValfsTer8), previously described only in two patients with Leigh syndrome. The patients presented here represent the largest group of subjects with <i>DNAJC30</i> gene mutations described to date. Based on our data, the autosomal recessive form of LHON caused by <i>DNAJC30</i> gene mutations is more frequent than the mitochondrial form in Polish patients. The results of our study suggest that Sanger sequencing of the single-exon <i>DNAJC30</i> gene should be a method of choice applied to identify a molecular background of clinically confirmed LHON in Polish patients. This approach will help to reduce the costs of molecular testing. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T20:40:54Z |
| publishDate | 2023-12-01 |
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| spelling | doaj.art-857ab4e71b654e248739c54600f93e0e2023-12-22T14:14:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0124241749610.3390/ijms242417496<i>DNAJC30</i> Gene Variants Are a Frequent Cause of a Rare Disease: Leber Hereditary Optic Neuropathy in Polish PatientsAnna Skorczyk-Werner0Katarzyna Tońska1Aleksandra Maciejczuk2Katarzyna Nowomiejska3Magdalena Korwin4Monika Ołdak5Anna Wawrocka6Maciej R. Krawczyński7Department of Medical Genetics, Poznan University of Medical Sciences, 60-806 Poznan, PolandInstitute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, 02-106 Warsaw, PolandInstitute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, 02-106 Warsaw, PolandDepartment of General and Pediatric Ophthalmology, Medical University of Lublin, 20-079 Lublin, PolandDepartment of Ophthalmology, Medical University of Warsaw, 02-005 Warsaw, PolandDepartment of Genetics, Institute of Physiology and Pathology of Hearing, 02-042 Warsaw, PolandDepartment of Medical Genetics, Poznan University of Medical Sciences, 60-806 Poznan, PolandDepartment of Medical Genetics, Poznan University of Medical Sciences, 60-806 Poznan, PolandLeber hereditary optic neuropathy (LHON) is a rare disorder causing a sudden painless loss of visual acuity in one or both eyes, affecting young males in their second to third decade of life. The molecular background of the LHON is up to 90%, genetically defined by a point mutation in mitochondrial DNA. Recently, an autosomal recessive form of LHON (LHONAR1, arLHON) has been discovered, caused by biallelic variants in the <i>DNAJC30</i> gene. This study provides the results of the <i>DNAJC30</i> gene analysis in a large group of 46 Polish patients diagnosed with LHON, together with the clinical characterization of the disease. The c.152A>G (p.Tyr51Cys) substitution in the <i>DNAJC30</i> gene was detected in all the patients as homozygote or compound heterozygote. Moreover, we identified one novel variant, c.293A>G, p.(Tyr98Cys), as well as two ultra-rare <i>DNAJC30</i> variants: c.293A>C, p.(Tyr98Ser), identified to date only in one individual affected with LHONAR1, and c.130_131delTC (p.Ser44ValfsTer8), previously described only in two patients with Leigh syndrome. The patients presented here represent the largest group of subjects with <i>DNAJC30</i> gene mutations described to date. Based on our data, the autosomal recessive form of LHON caused by <i>DNAJC30</i> gene mutations is more frequent than the mitochondrial form in Polish patients. The results of our study suggest that Sanger sequencing of the single-exon <i>DNAJC30</i> gene should be a method of choice applied to identify a molecular background of clinically confirmed LHON in Polish patients. This approach will help to reduce the costs of molecular testing.https://www.mdpi.com/1422-0067/24/24/17496Leber hereditary optic neuropathy (LHON)autosomal recessive LHON (LHONARarLHON)<i>DNAJC30</i>mtDNA (mitochondrial DNA) |
| spellingShingle | Anna Skorczyk-Werner Katarzyna Tońska Aleksandra Maciejczuk Katarzyna Nowomiejska Magdalena Korwin Monika Ołdak Anna Wawrocka Maciej R. Krawczyński <i>DNAJC30</i> Gene Variants Are a Frequent Cause of a Rare Disease: Leber Hereditary Optic Neuropathy in Polish Patients International Journal of Molecular Sciences Leber hereditary optic neuropathy (LHON) autosomal recessive LHON (LHONAR arLHON) <i>DNAJC30</i> mtDNA (mitochondrial DNA) |
| title | <i>DNAJC30</i> Gene Variants Are a Frequent Cause of a Rare Disease: Leber Hereditary Optic Neuropathy in Polish Patients |
| title_full | <i>DNAJC30</i> Gene Variants Are a Frequent Cause of a Rare Disease: Leber Hereditary Optic Neuropathy in Polish Patients |
| title_fullStr | <i>DNAJC30</i> Gene Variants Are a Frequent Cause of a Rare Disease: Leber Hereditary Optic Neuropathy in Polish Patients |
| title_full_unstemmed | <i>DNAJC30</i> Gene Variants Are a Frequent Cause of a Rare Disease: Leber Hereditary Optic Neuropathy in Polish Patients |
| title_short | <i>DNAJC30</i> Gene Variants Are a Frequent Cause of a Rare Disease: Leber Hereditary Optic Neuropathy in Polish Patients |
| title_sort | i dnajc30 i gene variants are a frequent cause of a rare disease leber hereditary optic neuropathy in polish patients |
| topic | Leber hereditary optic neuropathy (LHON) autosomal recessive LHON (LHONAR arLHON) <i>DNAJC30</i> mtDNA (mitochondrial DNA) |
| url | https://www.mdpi.com/1422-0067/24/24/17496 |
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