A novel autosomal recessive candidate gene responsible for rasopathy-like phenotype and bone marrow failure: rasa3

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dc.authorid0000-0001-6930-7148
dc.authorid0000-0002-1502-1600
dc.authorid0000-0002-9688-5223
dc.authorid0000-0002-9710-8653
dc.authorid0000-0003-0240-7691
dc.authorid0000-0002-0675-1839
dc.authorid0000-0002-0476-5452
dc.contributor.authorAyaz, Akif
dc.contributor.authorDoğru, Zeynep
dc.contributor.authorKök, Kıvanç
dc.contributor.authorBayram, Nihan
dc.contributor.authorYaman, Yöntem
dc.contributor.authorKöseoğlu, Abdullah Hüseyin
dc.contributor.authorYiğitbaşı, Türkan
dc.contributor.authorÖztürk Demir, Aslı Güner
dc.contributor.authorYüksel, Elçin
dc.contributor.authorDündar, Burcu
dc.contributor.authorÇaralan, Erdal Fırat
dc.contributor.authorNepesov, Serdar
dc.contributor.authorElli, Murat
dc.date.accessioned2024-08-28T07:02:32Z
dc.date.available2024-08-28T07:02:32Z
dc.date.issued2024
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Sağlık Bilim ve Teknolojileri Araştırma Enstitüsü
dc.departmentİstanbul Medipol Üniversitesi, Sağlık Bilimleri Enstitüsü, Genetik Hastalıklar Değerlendirme Merkezi (MEDİGEN)
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Çocuk Sağlığı ve Hastalıkları Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Tıbbi Genetik Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyokimya Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Biyoistatistik ve Tıp Bilişimi Ana Bilim Dalı
dc.description.abstractAlthough many genetic etiologies, such as Fanconi anemia, Shwachman-Diamond syndrome, dyskeratosis congenita, and Diamond-Blackfan anemia, from hereditary bone marrow failure are known today, the responsible gene remains unknown in a significant part of these patients. A 6-year-old girl, whose parents were first-cousin consanguineous, was referred to the pediatric hematology department due to growth retardation, thrombocytopenia, neutropenia, and anemia. The patient had low-set ears, pectus excavatum inferiorly, and cafe-au-lait spots. In whole-exome analysis, p.K385T (c.1154A > C) variant in the RASA3 gene was detected as homozygous. The amino acid position of the alteration is located in the conserved and ordered region, corresponding to the Ras GTPase activation domain (Ras-GAP) in the center of the protein. Importantly, most of in silico prediction tools of pathogenicity predicts the variant as damaging. RASopathies, which are characterized by many common clinical findings, such as atypical facial features, growth delays, and heart defects, are a group of rare genetic diseases caused by mutations in the genes involved in the Ras-MAPK pathway. The findings in this patient were consistent with the RASopathy-like phenotype and bone marrow failure. Interestingly, enrichment of RASopathy genes was observed in the RASA3 protein-protein interaction network. Furthermore, the subsequent topological clustering revealed a putative function module, which further implicates RASA3 in this disease as a novel potential causative gene. In this context, the detected RASA3 mutation could be manifesting itself clinically as the observed phenotype by disrupting the functional cooperation between the RASA3 protein and its interaction partners. Relatedly, current literature also supports the obtained findings. Overall, this study provides new insights into RASopathy and put forward the RASA3 gene as a novel candidate gene for this disease group.
dc.identifier.citationAyaz, A., Doğru, Z., Kök, K., Bayram, N., Yaman, Y., Köseoğlu, A. H. ... Elli, M. (2024). A novel autosomal recessive candidate gene responsible for rasopathy-like phenotype and bone marrow failure: rasa3. Journal of Pediatric Genetic, 13(3), 190-199. http://dx.doi.org/10.1055/s-0043-1771526
dc.identifier.doi10.1055/s-0043-1771526
dc.identifier.endpage199
dc.identifier.issn2146-4596
dc.identifier.issn2146-460X
dc.identifier.issue3
dc.identifier.pmid39086443
dc.identifier.startpage190
dc.identifier.urihttp://dx.doi.org/10.1055/s-0043-1771526
dc.identifier.urihttps://hdl.handle.net/20.500.12511/12785
dc.identifier.volume13
dc.identifier.wos001089385000001en_US
dc.identifier.wosqualityQ4
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakPubMed
dc.institutionauthorAyaz, Akif
dc.institutionauthorDoğru, Zeynep
dc.institutionauthorKök, Kıvanç
dc.institutionauthorBayram, Nihan
dc.institutionauthorYaman, Yöntem
dc.institutionauthorKöseoğlu, Abdullah Hüseyin
dc.institutionauthorYiğitbaşı, Türkan
dc.institutionauthorÖztürk Demir, Aslı Güner
dc.institutionauthorYüksel, Elçin
dc.institutionauthorDündar, Burcu
dc.institutionauthorÇaralan, Erdal Fırat
dc.institutionauthorNepesov, Serdar
dc.institutionauthorElli, Murat
dc.language.isoen
dc.relation.ispartofJournal of Pediatric Geneticen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectRASA3
dc.subjectRASopathy
dc.subjectBone Marrow Failure
dc.subjectP.K385T
dc.subjectC.1154A > C
dc.titleA novel autosomal recessive candidate gene responsible for rasopathy-like phenotype and bone marrow failure: rasa3
dc.typeArticle

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