Interferon-Induced Transmembrane Protein 5 Mutation Causing Type-V Osteogenesis Imperfecta

Mathew, Smitha; Santhanam, M. S.; Madhuri, Vrisha

doi:10.2106/jbjs.cc.n.00122

Cited by 2 publications

(2 citation statements)

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“…A recurrent heterozygous variant in the 5′UTR region of IFITM5 gene c.‐14C > T was observed in two patients with classical type V OI phenotype of hyperplastic callus, radial head dislocations, and interosseous membrane ossification (Mathew, Santhanam, & Madhuri, 2015).…”

Section: Discussionmentioning

confidence: 99%

Osteogenesis imperfecta: Novel genetic variants and clinical observations from a clinical exome study of 54 Indian patients

Madhuri

Selina

Loganathan

et al. 2020

Annals of Human Genetics

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Osteogenesis imperfecta (OI) is a group of inherited disorders with increased bone fragility and wide genetic heterogeneity. We report the outcome of clinical exome sequencing validated by Sanger sequencing in clinically diagnosed 54 OI patients in Indian population. In 52 patients, we report 20 new variants involving both dominant and recessive OI‐specific genes and correlate these with phenotypes. COL1A1 and COL1A2 gene variants were identified in 44.23%, of which 28.84% were glycine substitution abnormalities. Two novel compound heterozygous variants in the FKBP10 gene were seen in two unrelated probands. A novel heterogeneous duplication of chromosomal region chr17: 48268168–48278884 from exons 1–33 of the COL1A1 gene was found in one proband. In five probands, there were additional variants in association with OI. These were ANO5 in association with CRTAP in two probands of the same family causing gnathodiaphyseal dysplasia, COL5A2 with LEPRE1 causing Ehlers Danlos syndrome, COL11A1 in addition to COL1A1 causing Stickler syndrome, and a previously unreported combination of SLC34A1 gene variant with FKBP10 leading to Fanconi renal tubular syndrome type II. Our findings demonstrate the efficacy of clinical exome sequencing in screening OI patients, classifying its subtypes, and identifying associated disorders in consanguineous populations.

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Section: Discussionmentioning

confidence: 99%

Osteogenesis imperfecta: Novel genetic variants and clinical observations from a clinical exome study of 54 Indian patients

Madhuri

Selina

Loganathan

et al. 2020

Annals of Human Genetics

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“…Furthermore, IFITM5 is overexpressed in abnormal bone hyperplasia in rat primary osteoblasts, UMR106 rat osteosarcoma cells, human primary osteoblasts and Saos-2 human osteosarcoma cells [33][34][35]. There are already proven cases published about osteosarcoma occurring in osteogenesis imperfecta due to IFITM5 mutation [36,37]. The skeletal disorders caused by alterations in the IFITM5 gene, including c.-14C > T, c.119C > T (p.S40L), c.143A > G (p.N48S), while more case series are required to establish detailed genotype-phenotypes for these alterations in the IFITM5 gene [32,38].…”

Section: Discussionmentioning

confidence: 99%

Abnormal signal pathways and tumor heterogeneity in osteosarcoma

et al. 2023

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Background Osteosarcoma (OS) is the most frequent and aggressive primary malignant sarcoma among adolescents and chemotherapy has not substantially progressed for decades. New insights into OS development and therapeutic strategies are urgently needed. Methods We analyzed integrated single-cell transcriptomes, bulk RNA-seq, and microarray data from Gene Expression Omnibus (GEO) datasets. We also used Weighted Gene Co-expression Network Analysis (WGCNA), Gene set enrichment analysis (GSEA), and Gene set variation analysis (GSVA), along with Simple ClinVar and Enrichr web servers. Results The findings of integrated single-cell analysis showed that OS arises from imperfect osteogenesis during development. Novel abnormalities comprised deficient TGFβ and P53 signal pathways, and cell cycle pathway activation, and a potentially new driver mutation in the interferon induced transmembrane protein 5 (IFITM5) that might function as a pathogenic factor in OS. Osteosarcoma is characterized by oncocyte heterogeneity, especially in immunogenic and adipocyte-like subtypes that respectively promote and hamper OS treatment. Etoposide is a promising chemotherapeutic that provides palliation by affecting the subtype of OS and correcting the abnormal pathways. Conclusion Various abnormal signal pathways play indispensable roles in OS development. We explored the heterogeneity and underlying mechanisms of OS and generated findings that will assist with OS assessment and selecting optimal therapies.

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Interferon-Induced Transmembrane Protein 5 Mutation Causing Type-V Osteogenesis Imperfecta

Abstract: Although the differential diagnosis may include infantile cortical hypertrophy, child abuse, or a malignant tumor (e.g., osteosarcoma), the presence of typical clinical and radiographic features and characteristic gene mutation helps confirm the diagnosis of type-V osteogenesis imperfecta.

Cited by 2 publications

References 24 publications

Osteogenesis imperfecta: Novel genetic variants and clinical observations from a clinical exome study of 54 Indian patients

Osteogenesis imperfecta: Novel genetic variants and clinical observations from a clinical exome study of 54 Indian patients

Abnormal signal pathways and tumor heterogeneity in osteosarcoma

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