A novel de novo nonsense mutation in SALL4 causing duane radial ray syndrome: a case report and expanding the phenotypic spectrum
Abstract Background SALL4, a member of the SALL genes family, encodes a zinc-finger transcriptional factor that either activates or represses gene transcription depending on cell type during embryonic development. SALL4 mutations cause extremely variable conditions including Duane-radial ray (DRR),...
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | BMC Medical Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12920-023-01467-1 |
| _version_ | 1797863280898736128 |
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| author | Mobarakeh Ajam-Hosseini Farshid Parvini Abdolhamid Angaji |
| author_facet | Mobarakeh Ajam-Hosseini Farshid Parvini Abdolhamid Angaji |
| author_sort | Mobarakeh Ajam-Hosseini |
| collection | DOAJ |
| description | Abstract Background SALL4, a member of the SALL genes family, encodes a zinc-finger transcriptional factor that either activates or represses gene transcription depending on cell type during embryonic development. SALL4 mutations cause extremely variable conditions including Duane-radial ray (DRR), Okihiro, Holt-oram, Acro-renal ocular and IVIC syndromes, all with autosomal dominant inheritance pattern. However, all these syndromes with different terminologies are actually the same entity termed SALL4 related disorders. Case presentation Herein, we examine an Iranian patient suspected to DRR syndrome which has not been previously described in the population. Whole-exome sequencing (WES) was performed to examine pathogenic genes in the proband. Subsequently, Sanger sequencing was used to confirm the mutation found. To elucidate the effects of the identified mutation, clinical data of patient was collected. Morever, the possible impact of the mutation found on the corresponding protein was evaluated using bioinformatics tools. WES identifed a novel de novo heterozygous nonsense mutation in exon 2 of SALL4 gene (c.712 C > T:p.Q238X). Subsequently, segregation and phenotype-genotype correlation analysis as well as in-silico approaches confirmed the autosomal dominance inheritance and disease-causing nature of the identified mutation. In addition, studied patient had features not described previously, including kyphoscoliosis, dimple presacral sinus, barrel chest and artric disc (C6–C7). These manifestations could be additional characteristics of the growing phenotypic spectrum of SALL4 related disorders. Conclusion Our findings could extend the pathogenic mutations and phenotypic spectrum of SALL4 related disorders. Such reports can also aid to conduct genetic counseling, prenatal diagnosis and clinical management for individuals at high risk of SALL4 related disorders. |
| first_indexed | 2024-04-09T22:33:03Z |
| format | Article |
| id | doaj.art-98a75d36d88147f69080f87d5e0dc915 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-04-09T22:33:03Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-98a75d36d88147f69080f87d5e0dc9152023-03-22T12:38:04ZengBMCBMC Medical Genomics1755-87942023-02-011611710.1186/s12920-023-01467-1A novel de novo nonsense mutation in SALL4 causing duane radial ray syndrome: a case report and expanding the phenotypic spectrumMobarakeh Ajam-Hosseini0Farshid Parvini1Abdolhamid Angaji2Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Kharazmi UniversityDepartment of Biology, Faculty of Basic Sciences, Semnan UniversityDepartment of Cellular and Molecular Biology, Faculty of Biological Sciences, Kharazmi UniversityAbstract Background SALL4, a member of the SALL genes family, encodes a zinc-finger transcriptional factor that either activates or represses gene transcription depending on cell type during embryonic development. SALL4 mutations cause extremely variable conditions including Duane-radial ray (DRR), Okihiro, Holt-oram, Acro-renal ocular and IVIC syndromes, all with autosomal dominant inheritance pattern. However, all these syndromes with different terminologies are actually the same entity termed SALL4 related disorders. Case presentation Herein, we examine an Iranian patient suspected to DRR syndrome which has not been previously described in the population. Whole-exome sequencing (WES) was performed to examine pathogenic genes in the proband. Subsequently, Sanger sequencing was used to confirm the mutation found. To elucidate the effects of the identified mutation, clinical data of patient was collected. Morever, the possible impact of the mutation found on the corresponding protein was evaluated using bioinformatics tools. WES identifed a novel de novo heterozygous nonsense mutation in exon 2 of SALL4 gene (c.712 C > T:p.Q238X). Subsequently, segregation and phenotype-genotype correlation analysis as well as in-silico approaches confirmed the autosomal dominance inheritance and disease-causing nature of the identified mutation. In addition, studied patient had features not described previously, including kyphoscoliosis, dimple presacral sinus, barrel chest and artric disc (C6–C7). These manifestations could be additional characteristics of the growing phenotypic spectrum of SALL4 related disorders. Conclusion Our findings could extend the pathogenic mutations and phenotypic spectrum of SALL4 related disorders. Such reports can also aid to conduct genetic counseling, prenatal diagnosis and clinical management for individuals at high risk of SALL4 related disorders.https://doi.org/10.1186/s12920-023-01467-1SALL4 geneDuane-raidal rayCase reportNonsense mutationIran |
| spellingShingle | Mobarakeh Ajam-Hosseini Farshid Parvini Abdolhamid Angaji A novel de novo nonsense mutation in SALL4 causing duane radial ray syndrome: a case report and expanding the phenotypic spectrum BMC Medical Genomics SALL4 gene Duane-raidal ray Case report Nonsense mutation Iran |
| title | A novel de novo nonsense mutation in SALL4 causing duane radial ray syndrome: a case report and expanding the phenotypic spectrum |
| title_full | A novel de novo nonsense mutation in SALL4 causing duane radial ray syndrome: a case report and expanding the phenotypic spectrum |
| title_fullStr | A novel de novo nonsense mutation in SALL4 causing duane radial ray syndrome: a case report and expanding the phenotypic spectrum |
| title_full_unstemmed | A novel de novo nonsense mutation in SALL4 causing duane radial ray syndrome: a case report and expanding the phenotypic spectrum |
| title_short | A novel de novo nonsense mutation in SALL4 causing duane radial ray syndrome: a case report and expanding the phenotypic spectrum |
| title_sort | novel de novo nonsense mutation in sall4 causing duane radial ray syndrome a case report and expanding the phenotypic spectrum |
| topic | SALL4 gene Duane-raidal ray Case report Nonsense mutation Iran |
| url | https://doi.org/10.1186/s12920-023-01467-1 |
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