A Homozygous Nonsense Variant in UVSSA Causes UV-sensitive Syndrome from Very Large Kindred: The First Report from Iran
Background: Recessive disruptive mutations in nucleotide excision repair genes are responsible for a wide range of cutaneous photosensitivity and, in some cases, are associated with multi-system involvement. The heterogeneous nature of these conditions makes next-generation sequencing the method of...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2023-01-01
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| Series: | Advanced Biomedical Research |
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| Online Access: | http://www.advbiores.net/article.asp?issn=2277-9175;year=2023;volume=12;issue=1;spage=264;epage=264;aulast=Shadmehri |
| _version_ | 1797352361703768064 |
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| author | Azam Ahmadi Shadmehri Fahimeh Akbarian Azadeh Rahimi Mohammad Reza Pourreza Mohammad Amin Tabatabaiefar |
| author_facet | Azam Ahmadi Shadmehri Fahimeh Akbarian Azadeh Rahimi Mohammad Reza Pourreza Mohammad Amin Tabatabaiefar |
| author_sort | Azam Ahmadi Shadmehri |
| collection | DOAJ |
| description | Background: Recessive disruptive mutations in nucleotide excision repair genes are responsible for a wide range of cutaneous photosensitivity and, in some cases, are associated with multi-system involvement. The heterogeneous nature of these conditions makes next-generation sequencing the method of choice to detect disease-causing variants.
Materials and Methods: A patient from a large multiplex inbred Iranian kindred with several individuals suffering from skin sun-sensitive manifestations underwent complete clinical and molecular evaluations. Whole exome sequencing (WES) was performed on the genomic sample of the proband, followed by bioinformatics analysis. Subsequently, co-segregation of the candidate variant with the condition was performed by Sanger sequencing.
Results: A rare homozygous nonsense variant, c.1040G>A (p. Trp347*), was identified in the UVSSA gene, resulting in UV-sensitive syndrome (UVSS) complementation group A. The global minor allele frequency of the variant is < 0.001 in population databases. Tryptophan 347 residue is conserved among mammalians and vertebrates, and the null variant is believed to lead to a truncated protein with cellular mislocalization.
Conclusions: Here, we report the first genetic diagnosis of UVSS-A in Iran via the successful application of Next-generation sequencing, which expands our understanding of the molecular pathogenesis of this condition. |
| first_indexed | 2024-03-08T13:14:22Z |
| format | Article |
| id | doaj.art-6e104514212640ef981b8043a4f3a7e0 |
| institution | Directory Open Access Journal |
| issn | 2277-9175 |
| language | English |
| last_indexed | 2024-03-08T13:14:22Z |
| publishDate | 2023-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Advanced Biomedical Research |
| spelling | doaj.art-6e104514212640ef981b8043a4f3a7e02024-01-18T10:09:10ZengWolters Kluwer Medknow PublicationsAdvanced Biomedical Research2277-91752023-01-0112126426410.4103/abr.abr_45_22A Homozygous Nonsense Variant in UVSSA Causes UV-sensitive Syndrome from Very Large Kindred: The First Report from IranAzam Ahmadi ShadmehriFahimeh AkbarianAzadeh RahimiMohammad Reza PourrezaMohammad Amin TabatabaiefarBackground: Recessive disruptive mutations in nucleotide excision repair genes are responsible for a wide range of cutaneous photosensitivity and, in some cases, are associated with multi-system involvement. The heterogeneous nature of these conditions makes next-generation sequencing the method of choice to detect disease-causing variants. Materials and Methods: A patient from a large multiplex inbred Iranian kindred with several individuals suffering from skin sun-sensitive manifestations underwent complete clinical and molecular evaluations. Whole exome sequencing (WES) was performed on the genomic sample of the proband, followed by bioinformatics analysis. Subsequently, co-segregation of the candidate variant with the condition was performed by Sanger sequencing. Results: A rare homozygous nonsense variant, c.1040G>A (p. Trp347*), was identified in the UVSSA gene, resulting in UV-sensitive syndrome (UVSS) complementation group A. The global minor allele frequency of the variant is < 0.001 in population databases. Tryptophan 347 residue is conserved among mammalians and vertebrates, and the null variant is believed to lead to a truncated protein with cellular mislocalization. Conclusions: Here, we report the first genetic diagnosis of UVSS-A in Iran via the successful application of Next-generation sequencing, which expands our understanding of the molecular pathogenesis of this condition.http://www.advbiores.net/article.asp?issn=2277-9175;year=2023;volume=12;issue=1;spage=264;epage=264;aulast=Shadmehrihuman uvssa proteinirannonsense codonnucleotide excision repairuv-sensitive syndromewhole exome sequencing |
| spellingShingle | Azam Ahmadi Shadmehri Fahimeh Akbarian Azadeh Rahimi Mohammad Reza Pourreza Mohammad Amin Tabatabaiefar A Homozygous Nonsense Variant in UVSSA Causes UV-sensitive Syndrome from Very Large Kindred: The First Report from Iran Advanced Biomedical Research human uvssa protein iran nonsense codon nucleotide excision repair uv-sensitive syndrome whole exome sequencing |
| title | A Homozygous Nonsense Variant in UVSSA Causes UV-sensitive Syndrome from Very Large Kindred: The First Report from Iran |
| title_full | A Homozygous Nonsense Variant in UVSSA Causes UV-sensitive Syndrome from Very Large Kindred: The First Report from Iran |
| title_fullStr | A Homozygous Nonsense Variant in UVSSA Causes UV-sensitive Syndrome from Very Large Kindred: The First Report from Iran |
| title_full_unstemmed | A Homozygous Nonsense Variant in UVSSA Causes UV-sensitive Syndrome from Very Large Kindred: The First Report from Iran |
| title_short | A Homozygous Nonsense Variant in UVSSA Causes UV-sensitive Syndrome from Very Large Kindred: The First Report from Iran |
| title_sort | homozygous nonsense variant in uvssa causes uv sensitive syndrome from very large kindred the first report from iran |
| topic | human uvssa protein iran nonsense codon nucleotide excision repair uv-sensitive syndrome whole exome sequencing |
| url | http://www.advbiores.net/article.asp?issn=2277-9175;year=2023;volume=12;issue=1;spage=264;epage=264;aulast=Shadmehri |
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