A Single Recurrent Mutation in the 5′-UTR of IFITM5 Causes Osteogenesis Imperfecta Type V

Cho, Tae-Joon; Lee, Kyung-Eun; Lee, Sook-Kyung; Song, Su Jeong; Kim, Kyung Jin; Jeon, D.; Lee, Gene; Kim, Ha‐Neui; Lee, Hye Ran; Eom, Hye-Hyun; Lee, Zang Hee; Kim, Ok-Hwa; Park, Woong-Yang; Park, Sung Sup; Ikegawa, Shiro; Yoo, Won Joon; Choi, In Ho; Kim, Jung-Wook

doi:10.1016/j.ajhg.2012.06.005

Cited by 228 publications

(230 citation statements)

References 16 publications

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“…Indeed, 5'-UTR mutations have already been reported as the cause of diseases including OI (Cho et al, 2012;Semler et al, 2012;Shaheen et al, 2012, Caparrós-Martin et al, 2013. However, because the second mutation in patient P.5 was not identified, and this change is localized in a non-coding region, we suggest that the c.-190A>G change is not a disease-causing mutation.…”

Section: Discussionmentioning

confidence: 71%

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Analysis of FKBP10, SERPINH1, and SERPINF1 genes in patients with osteogenesis imperfecta

et al. 2016

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ABSTRACT. Osteogenesis imperfecta (OI) is a heterogeneous disorder that causes fragility, deformity, and fractures in bones. A large number of genes that are associated with the disease have been identified in the last decade; this makes the genetic diagnosis of OI more difficult. To improve our knowledge of the genetic mutation profile in OI we used single-stranded conformation polymorphism screening and automated sequencing to investigate the SERPINH1, FKBP10, and SERPINF1 genes, which are related to recessive OI, in 23 unrelated Brazilian patients. Nine rare changes and four common polymorphisms were detected. Most changes were benign genetic variants. In general, changes in the SERPINH1 and SERPINF1 genes were synonymous polymorphisms or missense changes located in non-coding regions. A pathogenic change was found in the FKBP10 gene. The characterization of mutations related to OI in distinct populations can improve our knowledge of the genetic aspects of OI and help us develop molecular strategies for the diagnosis of the disease.

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Section: Discussionmentioning

confidence: 71%

“…Recently, dominant autosomal mutations have also been detected in OI patients that carry genetic changes in the IFITM5 gene. This gene codes for an osteoblast-specific transmembrane protein that appears to be associated with bone mineralization (Moffatt et al, 2008;Cho et al, 2012;Semler et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Analysis of FKBP10, SERPINH1, and SERPINF1 genes in patients with osteogenesis imperfecta

et al. 2016

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“…Most commonly, OI is an autosomal dominant condition caused by mutations in COL1A1 and COL1A2 leading to clinical forms I to IV (25). Type V OI has recently been shown to be caused by mutations in IFITM5, also transmitted in an autosomal dominant pattern; the exact role of IFITM5 in determining bone strength remains elusive (26,27). Several rarer forms of OI with autosomal recessive inheritance exist, and the list of candidate genes for such phenotypes is ever increasing (Table 1).…”

Section: Monogenic Diseases Affecting the Bone Matrixmentioning

confidence: 99%

Genetics of osteoporosis: searching for candidate genes for bone fragility

Rocha-Braz

Ferraz-de-Souza

2016

Arch. Endocrinol. Metab.

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The pathogenesis of osteoporosis, a common disease with great morbidity and mortality, comprises environmental and genetic factors. As with other complex disorders, the genetic basis of osteoporosis has been difficult to identify. Nevertheless, several approaches have been undertaken in the past decades in order to identify candidate genes for bone fragility, including the study of rare monogenic syndromes with striking bone phenotypes (e.g. osteogenesis imperfecta and osteopetroses), the analysis of individuals or families with extreme osteoporotic phenotypes (e.g. idiopathic juvenile and pregnancy-related osteoporosis), and, chiefly, genome-wide association studies (GWAS) in large populations. Altogether, these efforts have greatly increased the understanding of molecular mechanisms behind bone remodelling, which has rapidly translated into the development of novel therapeutic strategies, exemplified by the tales of cathepsin K (CTSK) and sclerostin (SOST). Additional biological evidence of involvement in bone physiology still lacks for several candidate genes arisen from GWAS, opening an opportunity for the discovery of new mechanisms regulating bone strength, particularly with the advent of high-throughput genomic technologies. In this review, candidate genes for bone fragility will be presented in comprehensive tables and discussed with regard to how their association with osteoporosis emerged, highlighting key players such as LRP5, WNT1 and PLS3. Current limitations in our understanding of the genetic contribution to osteoporosis, such as yet unidentified genetic modifiers, may be overcome in the near future with better genotypic and phenotypic characterisation of large populations and the detailed study of candidate genes in informative individuals with marked phenotype. Arch Endocrinol Metab. 2016;60(4):391-401

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“…in the remaining 10% of cases, oi is the result of recessive mutations in iFiTm5 (interferon-induced transmembrane protein 5, oi type V; bone formation co-participant) (ref. 10 ). recently, mutations in the WNT1 gene (Winglesstype mmTV integration site family, member 1, bone mass regulator) have been described in patients diagnosed with oi type iV (ref.…”

Section: Introductionmentioning

confidence: 99%

Eight mutations including 5 novel ones in the COL1A1 gene in Czech patients with osteogenesis imperfecta

Hrušková¹,

Fijałkowski²,

Hul³

et al. 2016

BIOMED PAP

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a Background and Aim. Osteogenesis imperfecta (OI), also called brittle bone disease, is a clinically and genetically heterogeneous disorder characterized by decreased bone density. Autosomal dominant forms result from mutations in either the COL1A1 (collagen type I alpha-1 chain) or COL1A2 (collagen type I alpha-2 chain) genes encoding the type I collagen. The aim of this study was to identify mutations and allelic variants of the COL1A1 gene in patients with osteogenesis imperfecta (OI). Methods and Results. Molecular genetic analysis of the COL1A1 gene was performed in a cohort of 34 patients with OI. The DNA samples were analysed by PCR and Sanger sequencing. DNA changes in coding sequences of the gene were compared with Type 1 Collagen Mutation Database. Genetic variants resulting in either quantitatively or structurally defective protein production were found in 6 unrelated patients. Four identified mutations are connected to decreased protein production (Tyr47X, Arg131X, Arg415X, Gln1341X), 2 result in amino acid substitution (Cys61Phe, Pro1186Ala) and the last affects splicing (c.1057-1G>T). Further, one silent mutation (Gly794Gly) was detected. No protein analysis was performed. Conclusion. Of the 8 identified mutations, 5 were novel and have not been reported before. Only one causes substitution of glycine located within the Gly-X-Y triplets in the triple helical domain. Two mutations are located in major ligand binding regions (MLBR) which are important for bone strength and flexibility. Although the genotype-phenotype correlation is still unclear, our findings should contribute to elucidating this relationship in patients diagnosed with OI.

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A Single Recurrent Mutation in the 5′-UTR of IFITM5 Causes Osteogenesis Imperfecta Type V

Cited by 228 publications

References 16 publications

Analysis of FKBP10, SERPINH1, and SERPINF1 genes in patients with osteogenesis imperfecta

Analysis of FKBP10, SERPINH1, and SERPINF1 genes in patients with osteogenesis imperfecta

Genetics of osteoporosis: searching for candidate genes for bone fragility

Eight mutations including 5 novel ones in the COL1A1 gene in Czech patients with osteogenesis imperfecta

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