Truncated SPAG9 as a novel candidate gene for a new syndrome: Coarse facial features, albinism, cataract and developmental delay (CACD syndrome)
Abstract Sperm-associated antigen 9 (SPAG9) is a member of cancer-testis antigen, having characteristics of a scaffold protein, which is involved in the c-Jun N-terminal kinase JNK signaling pathway, suggesting its key involvement in different physiological processes, such as survival, apoptosis, tu...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Sociedade Brasileira de Genética
2025-01-01
|
| Series: | Genetics and Molecular Biology |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572025000100102&lng=en&tlng=en |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832592474162331648 |
|---|---|
| author | Majid Alfadhel Bashayr S. Alhubayshi Muhammad Umair Ahmed Alfaidi Deemah Alwadaani Essra Aloyouni Safdar Abbas Abdulkareem Al Abdulrahman Mohammed Aldrees Abeer Al Tuwaijri Ruaa S. Alharithy Abdulaziz Alajlan Abdulrahman Alswaid Saad Almohrij Sultan Al-Khenaizan |
| author_facet | Majid Alfadhel Bashayr S. Alhubayshi Muhammad Umair Ahmed Alfaidi Deemah Alwadaani Essra Aloyouni Safdar Abbas Abdulkareem Al Abdulrahman Mohammed Aldrees Abeer Al Tuwaijri Ruaa S. Alharithy Abdulaziz Alajlan Abdulrahman Alswaid Saad Almohrij Sultan Al-Khenaizan |
| author_sort | Majid Alfadhel |
| collection | DOAJ |
| description | Abstract Sperm-associated antigen 9 (SPAG9) is a member of cancer-testis antigen, having characteristics of a scaffold protein, which is involved in the c-Jun N-terminal kinase JNK signaling pathway, suggesting its key involvement in different physiological processes, such as survival, apoptosis, tumorigenesis, and cell proliferation. We identified two families (A and B) having multisystem features like coarse facial features, albinism, cataracts, skeletal abnormalities, and developmental delay. Whole genome sequencing (WGS) in families A and B revealed a homozygous frameshift variant (c.903del; p.Phe301Leufs*2) in the SPAG9 gene. Sanger sequencing of both families revealed perfect segregation of the identified variant in all family members. 3D protein modeling revealed substantial changes in the protein’s secondary structure. Furthermore, RT-qPCR revealed a substantial reduction of SPAG9 gene expression at the mRNA level in the affected individuals of both families, thus supporting the pathogenic nature of the identified variant. For the first time in the literature, biallelic SPAG9 gene variation was linked to multisystem-exhibiting features like coarse facial features, albinism, cataracts, skeletal abnormalities, and developmental delay. Thus, this data supports the notion that SPAG9 plays an important role in a multisystemic disorder in humans. |
| format | Article |
| id | doaj-art-f3fa9de39bd9450ca8861ef33fd5910d |
| institution | Kabale University |
| issn | 1678-4685 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Sociedade Brasileira de Genética |
| record_format | Article |
| series | Genetics and Molecular Biology |
| spelling | doaj-art-f3fa9de39bd9450ca8861ef33fd5910d2025-01-21T07:45:02ZengSociedade Brasileira de GenéticaGenetics and Molecular Biology1678-46852025-01-0148110.1590/1678-4685-gmb-2024-0094Truncated SPAG9 as a novel candidate gene for a new syndrome: Coarse facial features, albinism, cataract and developmental delay (CACD syndrome)Majid Alfadhelhttps://orcid.org/0000-0002-9427-7240Bashayr S. AlhubayshiMuhammad UmairAhmed AlfaidiDeemah AlwadaaniEssra AloyouniSafdar AbbasAbdulkareem Al AbdulrahmanMohammed AldreesAbeer Al TuwaijriRuaa S. AlharithyAbdulaziz AlajlanAbdulrahman AlswaidSaad AlmohrijSultan Al-KhenaizanAbstract Sperm-associated antigen 9 (SPAG9) is a member of cancer-testis antigen, having characteristics of a scaffold protein, which is involved in the c-Jun N-terminal kinase JNK signaling pathway, suggesting its key involvement in different physiological processes, such as survival, apoptosis, tumorigenesis, and cell proliferation. We identified two families (A and B) having multisystem features like coarse facial features, albinism, cataracts, skeletal abnormalities, and developmental delay. Whole genome sequencing (WGS) in families A and B revealed a homozygous frameshift variant (c.903del; p.Phe301Leufs*2) in the SPAG9 gene. Sanger sequencing of both families revealed perfect segregation of the identified variant in all family members. 3D protein modeling revealed substantial changes in the protein’s secondary structure. Furthermore, RT-qPCR revealed a substantial reduction of SPAG9 gene expression at the mRNA level in the affected individuals of both families, thus supporting the pathogenic nature of the identified variant. For the first time in the literature, biallelic SPAG9 gene variation was linked to multisystem-exhibiting features like coarse facial features, albinism, cataracts, skeletal abnormalities, and developmental delay. Thus, this data supports the notion that SPAG9 plays an important role in a multisystemic disorder in humans.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572025000100102&lng=en&tlng=enSPAG9oculocutaneous albinismintellectual disabilitycataractframeshift variant |
| spellingShingle | Majid Alfadhel Bashayr S. Alhubayshi Muhammad Umair Ahmed Alfaidi Deemah Alwadaani Essra Aloyouni Safdar Abbas Abdulkareem Al Abdulrahman Mohammed Aldrees Abeer Al Tuwaijri Ruaa S. Alharithy Abdulaziz Alajlan Abdulrahman Alswaid Saad Almohrij Sultan Al-Khenaizan Truncated SPAG9 as a novel candidate gene for a new syndrome: Coarse facial features, albinism, cataract and developmental delay (CACD syndrome) Genetics and Molecular Biology SPAG9 oculocutaneous albinism intellectual disability cataract frameshift variant |
| title | Truncated SPAG9 as a novel candidate gene for a new syndrome: Coarse facial features, albinism, cataract and developmental delay (CACD syndrome) |
| title_full | Truncated SPAG9 as a novel candidate gene for a new syndrome: Coarse facial features, albinism, cataract and developmental delay (CACD syndrome) |
| title_fullStr | Truncated SPAG9 as a novel candidate gene for a new syndrome: Coarse facial features, albinism, cataract and developmental delay (CACD syndrome) |
| title_full_unstemmed | Truncated SPAG9 as a novel candidate gene for a new syndrome: Coarse facial features, albinism, cataract and developmental delay (CACD syndrome) |
| title_short | Truncated SPAG9 as a novel candidate gene for a new syndrome: Coarse facial features, albinism, cataract and developmental delay (CACD syndrome) |
| title_sort | truncated spag9 as a novel candidate gene for a new syndrome coarse facial features albinism cataract and developmental delay cacd syndrome |
| topic | SPAG9 oculocutaneous albinism intellectual disability cataract frameshift variant |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572025000100102&lng=en&tlng=en |
| work_keys_str_mv | AT majidalfadhel truncatedspag9asanovelcandidategeneforanewsyndromecoarsefacialfeaturesalbinismcataractanddevelopmentaldelaycacdsyndrome AT bashayrsalhubayshi truncatedspag9asanovelcandidategeneforanewsyndromecoarsefacialfeaturesalbinismcataractanddevelopmentaldelaycacdsyndrome AT muhammadumair truncatedspag9asanovelcandidategeneforanewsyndromecoarsefacialfeaturesalbinismcataractanddevelopmentaldelaycacdsyndrome AT ahmedalfaidi truncatedspag9asanovelcandidategeneforanewsyndromecoarsefacialfeaturesalbinismcataractanddevelopmentaldelaycacdsyndrome AT deemahalwadaani truncatedspag9asanovelcandidategeneforanewsyndromecoarsefacialfeaturesalbinismcataractanddevelopmentaldelaycacdsyndrome AT essraaloyouni truncatedspag9asanovelcandidategeneforanewsyndromecoarsefacialfeaturesalbinismcataractanddevelopmentaldelaycacdsyndrome AT safdarabbas truncatedspag9asanovelcandidategeneforanewsyndromecoarsefacialfeaturesalbinismcataractanddevelopmentaldelaycacdsyndrome AT abdulkareemalabdulrahman truncatedspag9asanovelcandidategeneforanewsyndromecoarsefacialfeaturesalbinismcataractanddevelopmentaldelaycacdsyndrome AT mohammedaldrees truncatedspag9asanovelcandidategeneforanewsyndromecoarsefacialfeaturesalbinismcataractanddevelopmentaldelaycacdsyndrome AT abeeraltuwaijri truncatedspag9asanovelcandidategeneforanewsyndromecoarsefacialfeaturesalbinismcataractanddevelopmentaldelaycacdsyndrome AT ruaasalharithy truncatedspag9asanovelcandidategeneforanewsyndromecoarsefacialfeaturesalbinismcataractanddevelopmentaldelaycacdsyndrome AT abdulazizalajlan truncatedspag9asanovelcandidategeneforanewsyndromecoarsefacialfeaturesalbinismcataractanddevelopmentaldelaycacdsyndrome AT abdulrahmanalswaid truncatedspag9asanovelcandidategeneforanewsyndromecoarsefacialfeaturesalbinismcataractanddevelopmentaldelaycacdsyndrome AT saadalmohrij truncatedspag9asanovelcandidategeneforanewsyndromecoarsefacialfeaturesalbinismcataractanddevelopmentaldelaycacdsyndrome AT sultanalkhenaizan truncatedspag9asanovelcandidategeneforanewsyndromecoarsefacialfeaturesalbinismcataractanddevelopmentaldelaycacdsyndrome |