Basit öğe kaydını göster

dc.contributor.authorAkman, Yunus Emre
dc.contributor.authorGeyik, Filiz
dc.contributor.authorKURUĞOĞLU, SEBUH
dc.contributor.authorVURAL, ZEKERİYYA MEHMET
dc.contributor.authorBilguvar, Kaya
dc.contributor.authorTÜYSÜZ, BEYHAN
dc.contributor.authorULUDAĞ ALKAYA, DİLEK
dc.contributor.authorALAYLIOĞLU, MERVE
dc.contributor.authorKasap, Busra
dc.date.accessioned2023-10-10T10:47:00Z
dc.date.available2023-10-10T10:47:00Z
dc.identifier.citationTÜYSÜZ B., ULUDAĞ ALKAYA D., Geyik F., ALAYLIOĞLU M., Kasap B., KURUĞOĞLU S., Akman Y. E., VURAL Z. M., Bilguvar K., "Biallelic frameshift variants in PHLDB1 cause mild-type osteogenesis imperfecta with regressive spondylometaphyseal changes", JOURNAL OF MEDICAL GENETICS, 2022
dc.identifier.issn0022-2593
dc.identifier.othervv_1032021
dc.identifier.otherav_0c2f29c9-7236-463b-8008-540909fad5bb
dc.identifier.urihttp://hdl.handle.net/20.500.12627/189506
dc.identifier.urihttps://doi.org/10.1136/jmg-2022-108763
dc.description.abstractBackgroundOsteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders characterised by susceptibility to fractures, primarily due to defects in type 1 collagen. The aim of this study is to present a novel OI phenotype and its causative candidate gene. MethodsWhole-exome sequencing and clinical evaluation were performed in five patients from two unrelated families. PHLDB1 mRNA expression in blood and fibroblasts was investigated by real-time PCR, and western blot analysis was further performed on skin fibroblasts. ResultsThe common findings among the five affected children were recurrent fractures and/or osteopaenia, platyspondyly, short and bowed long bones, and widened metaphyses. Metaphyseal and vertebral changes regressed after early childhood, and no fractures occurred under bisphosphonate treatment. We identified biallelic NM_001144758.3:c.2392dup and NM_001144758.3:c.2690_2693del pathogenic variants in PHLDB1 in the affected patients, respectively, in the families; parents were heterozygous for these variants. PHLDB1 encodes pleckstrin homology-like domain family B member-1 (PHLDB1) protein, which has a role in insulin-dependent Akt phosphorylation. Compared with controls, a decrease in the expression levels of PHLDB1 in the blood and skin fibroblast samples was detected. Western blot analysis of cultured fibroblasts further confirmed the loss of PHLDB1. ConclusionTwo biallelic frameshift variants in the candidate gene PHLDB1 were identified in independent families with a novel, mild-type, autosomal recessive OI. The demonstration of decreased PHLDB1 mRNA expression levels in blood and fibroblast samples supports the hypothesis that PHLDB1 pathogenic variants are causative for the observed phenotype.
dc.language.isoeng
dc.subjectSağlık Bilimleri
dc.subjectTemel Bilimler
dc.subjectGenetik (klinik)
dc.subjectMoleküler Biyoloji
dc.subjectGenetik
dc.subjectTıbbi Genetik
dc.subjectYaşam Bilimleri
dc.subjectDahili Tıp Bilimleri
dc.subjectTıp
dc.subjectYaşam Bilimleri (LIFE)
dc.subjectMoleküler Biyoloji ve Genetik
dc.subjectGENETİK VE KALITIM
dc.titleBiallelic frameshift variants in PHLDB1 cause mild-type osteogenesis imperfecta with regressive spondylometaphyseal changes
dc.typeMakale
dc.relation.journalJOURNAL OF MEDICAL GENETICS
dc.contributor.departmentİstanbul Üniversitesi-Cerrahpaşa , Cerrahpaşa Tıp Fakültesi , Dahili Tıp Bilimleri Bölümü
dc.contributor.firstauthorID4309575


Bu öğenin dosyaları:

DosyalarBoyutBiçimGöster

Bu öğe ile ilişkili dosya yok.

Bu öğe aşağıdaki koleksiyon(lar)da görünmektedir.

Basit öğe kaydını göster