Clinical characterizations and molecular genetic study of two co-segregating variants in PDZD7 and PDE6C genes leading simultaneously to non-syndromic hearing loss and achromatopsia
Abstract Background Autosomal recessive non-syndromic hearing loss (NSHL) and cone dystrophies (CODs) are highly genetically and phenotypically heterogeneous disorders. In this study, we applied the whole exome sequencing (WES) to find the cause of HL and COD in an Iranian consanguineous family with...
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BMC
2024-07-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-024-01942-3 |
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| author | Zahra Nouri Akram Sarmadi Sina Narrei Hamidreza Kianersi Farzan Kianersi Mohammad Amin Tabatabaiefar |
| author_facet | Zahra Nouri Akram Sarmadi Sina Narrei Hamidreza Kianersi Farzan Kianersi Mohammad Amin Tabatabaiefar |
| author_sort | Zahra Nouri |
| collection | DOAJ |
| description | Abstract Background Autosomal recessive non-syndromic hearing loss (NSHL) and cone dystrophies (CODs) are highly genetically and phenotypically heterogeneous disorders. In this study, we applied the whole exome sequencing (WES) to find the cause of HL and COD in an Iranian consanguineous family with three affected individuals. Methods Three members from an Iranian consanguineous family who were suffering from NSHL and visual impairment were ascertained in this study. Comprehensive clinical evaluations and genetic analysis followed by bioinformatic and co-segregation studies were performed to diagnose the cause of these phenotypes. Data were collected from 2020 to 2022. Results All cases showed congenital bilateral NSHL, decreased visual acuity, poor color discrimination, photophobia and macular atrophy. Moreover, cornea, iris and anterior vitreous were within normal limit in both eyes, decreased foveal sensitivity, central scotoma and generalized depression of visual field were seen in three cases. WES results showed two variants, a novel null variant (p.Trp548Ter) in the PDE6C gene causing COD type 4 (Achromatopsia) and a previously reported variant (p.Ile84Thr) in the PDZD7 gene causing NSHL. Both variants were found in the cis configuration on chromosome 10 with a genetic distance of about 8.3 cM, leading to their co-inheritance. However, two diseases could appear independently in subsequent generations due to crossover during meiosis. Conclusions Here, we could successfully determine the etiology of a seemingly complex phenotype in two adjacent genes. We identified a novel variant in the PDE6C gene, related to achromatopsia. Interestingly, this variant could cooperatively cause visual disorders: cone dystrophy and cone-rod dystrophy. |
| format | Article |
| id | doaj-art-0953796e171344b2b31b2ac8dbdb4ba3 |
| institution | DOAJ |
| issn | 1755-8794 |
| language | English |
| publishDate | 2024-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj-art-0953796e171344b2b31b2ac8dbdb4ba32025-08-20T03:06:43ZengBMCBMC Medical Genomics1755-87942024-07-0117111010.1186/s12920-024-01942-3Clinical characterizations and molecular genetic study of two co-segregating variants in PDZD7 and PDE6C genes leading simultaneously to non-syndromic hearing loss and achromatopsiaZahra Nouri0Akram Sarmadi1Sina Narrei2Hamidreza Kianersi3Farzan Kianersi4Mohammad Amin Tabatabaiefar5Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical SciencesDepartment of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical SciencesDepartment of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical SciencesIsfahan Eye Research Center, Isfahan University of Medical SciencesDepartment of Ophthalmology, Isfahan University of Medical SciencesDepartment of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical SciencesAbstract Background Autosomal recessive non-syndromic hearing loss (NSHL) and cone dystrophies (CODs) are highly genetically and phenotypically heterogeneous disorders. In this study, we applied the whole exome sequencing (WES) to find the cause of HL and COD in an Iranian consanguineous family with three affected individuals. Methods Three members from an Iranian consanguineous family who were suffering from NSHL and visual impairment were ascertained in this study. Comprehensive clinical evaluations and genetic analysis followed by bioinformatic and co-segregation studies were performed to diagnose the cause of these phenotypes. Data were collected from 2020 to 2022. Results All cases showed congenital bilateral NSHL, decreased visual acuity, poor color discrimination, photophobia and macular atrophy. Moreover, cornea, iris and anterior vitreous were within normal limit in both eyes, decreased foveal sensitivity, central scotoma and generalized depression of visual field were seen in three cases. WES results showed two variants, a novel null variant (p.Trp548Ter) in the PDE6C gene causing COD type 4 (Achromatopsia) and a previously reported variant (p.Ile84Thr) in the PDZD7 gene causing NSHL. Both variants were found in the cis configuration on chromosome 10 with a genetic distance of about 8.3 cM, leading to their co-inheritance. However, two diseases could appear independently in subsequent generations due to crossover during meiosis. Conclusions Here, we could successfully determine the etiology of a seemingly complex phenotype in two adjacent genes. We identified a novel variant in the PDE6C gene, related to achromatopsia. Interestingly, this variant could cooperatively cause visual disorders: cone dystrophy and cone-rod dystrophy.https://doi.org/10.1186/s12920-024-01942-3Hearing lossCone dystrophyAchromatopsiaWhole exome sequencingPDZD7PDE6C |
| spellingShingle | Zahra Nouri Akram Sarmadi Sina Narrei Hamidreza Kianersi Farzan Kianersi Mohammad Amin Tabatabaiefar Clinical characterizations and molecular genetic study of two co-segregating variants in PDZD7 and PDE6C genes leading simultaneously to non-syndromic hearing loss and achromatopsia BMC Medical Genomics Hearing loss Cone dystrophy Achromatopsia Whole exome sequencing PDZD7 PDE6C |
| title | Clinical characterizations and molecular genetic study of two co-segregating variants in PDZD7 and PDE6C genes leading simultaneously to non-syndromic hearing loss and achromatopsia |
| title_full | Clinical characterizations and molecular genetic study of two co-segregating variants in PDZD7 and PDE6C genes leading simultaneously to non-syndromic hearing loss and achromatopsia |
| title_fullStr | Clinical characterizations and molecular genetic study of two co-segregating variants in PDZD7 and PDE6C genes leading simultaneously to non-syndromic hearing loss and achromatopsia |
| title_full_unstemmed | Clinical characterizations and molecular genetic study of two co-segregating variants in PDZD7 and PDE6C genes leading simultaneously to non-syndromic hearing loss and achromatopsia |
| title_short | Clinical characterizations and molecular genetic study of two co-segregating variants in PDZD7 and PDE6C genes leading simultaneously to non-syndromic hearing loss and achromatopsia |
| title_sort | clinical characterizations and molecular genetic study of two co segregating variants in pdzd7 and pde6c genes leading simultaneously to non syndromic hearing loss and achromatopsia |
| topic | Hearing loss Cone dystrophy Achromatopsia Whole exome sequencing PDZD7 PDE6C |
| url | https://doi.org/10.1186/s12920-024-01942-3 |
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