Clinical and Molecular Characterization of Osteogenesis Imperfecta Type V

Brizola, Evelise; Mattos, Eduardo Preusser de; Ferrari, Jéssica Tonin; Freire, Patricia O.A.; Germer, Raquel; Llerena, Juan Clinton; Félix, Têmis Maria

doi:10.1159/000439506

Cited by 24 publications

(17 citation statements)

References 26 publications

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“…The absence of DI in OI type V has been reported in the first description of the disorder (10) and has also been noted in subsequent case series (16, 17, 27). This could be explained by the lack of a collagen type I defect in OI type V, as collagen type I is the major protein of intertubular dentin (90%) (28).…”

Section: Discussionsupporting

confidence: 59%

Dental and facial characteristics of osteogenesis imperfecta type V

Retrouvey

Taqi

Tamimi

et al. 2018

Preprint

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Osteogenesis imperfecta (OI) type V is an ultrarare heritable bone disorder caused by the heterozygous c.-14C>T mutation in IFITM5. The dental and craniofacial phenotype has not been described in detail. In the present multicenter study (Brittle Bone Disease Consortium) 14 individuals with OI type V (age 3 to 50 years; 10 females, 4 males) underwent dental and craniofacial assessment. None of the individuals had dentinogenesis imperfecta. Six of the 9 study participants (66%) for whom panoramic radiographs were obtained had at least one missing tooth (range 1 to 9). Class II molar occlusion was present in 8 (57%) of the 14 study participants. The facial profile was retrusive and lower face height was decreased in 8 (57%) individuals. Cephalometry, performed in three study participants, revealed a severely retrusive maxilla and mandible, and poorly angulated incisors in a 14-year old girl, a protrusive maxilla and a retrusive mandible in a 14-year old boy. Cone beam computed tomograpy scans were obtained from two study participants and demonstrated intervertebral disc calcification at the C2-C3 level in one individual. Our study observed that OI type V is associated with missing permanent teeth, especially permanent premolar, but not with dentinogenesis imperfecta. The pattern of craniofacial abnormalities in OI type V thus differs from that in other severe OI types, such as OI type III and IV, and could be described as a bimaxillary retrusive malocclusion with reduced lower face height and multiple missing teeth.

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Section: Discussionsupporting

confidence: 59%

Dental and facial characteristics of osteogenesis imperfecta type V

Retrouvey

Taqi

Tamimi

et al. 2018

Preprint

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“…BRIL is expressed in osteoblasts and may play a role in early mineralization stages . A recurrent point mutation ( IFITM5 c.–14C>T) was identified in the 5′‐untranslated region (5′UTR) of the IFITM5 gene and was later confirmed in other OI type V patient cohorts . The mutation results in the addition of five amino acid residues (MALEP) at the N terminus of BRIL and to an apparent gain of function .…”

Section: Introductionmentioning

confidence: 99%

“…(15,16) A recurrent point mutation (IFITM5 c.-14C>T) was identified in the 5 0 -untranslated region (5 0 UTR) of the IFITM5 gene and was later confirmed in other OI type V patient cohorts. (5,10,12,13,17,18) The mutation results in the addition of five amino acid residues (MALEP) at the N terminus of BRIL and to an apparent gain of function. (13) It has to be noted that a nonclassical IFITM5 mutation (c.119C>T; p. S40L) has been recently described as causing very severe OI phenotype with prenatal onset and showing an OI type VI rather than OI type V bone phenotype.…”

Section: Introductionmentioning

confidence: 99%

Hypermineralization and High Osteocyte Lacunar Density in Osteogenesis Imperfecta Type V Bone Indicate Exuberant Primary Bone Formation

Blouin

Fratzl‐Zelman

Glorieux

et al. 2017

Journal of Bone and Mineral Research

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In contrast to “classical” forms of Osteogenesis imperfecta (OI) types I to IV, caused by a mutation in COL1A1/A2, OI type V is due to a gain-of-function mutation in the IFITM5 gene, encoding the interferon-induced transmembrane protein 5, or bone-restricted ifitm-like protein (BRIL). Its phenotype distinctly differs from OI types I to IV by absence of blue sclerae and dentinogenesis imperfecta, by the occurrence of ossification disorders like hyperplastic callus and forearm interosseous membrane ossification. Little is known about the impact of the mutation on bone tissue/material level in untreated and bisphosphonate treated patients. Therefore investigations of transiliac bone biopsy samples from a cohort of OI type V children (n=15, 8.7±4 years old) untreated at baseline and a subset (n=8) after pamidronate treatment (2.6 years in average) were performed. Quantitative backscattered electron imaging (qBEI) was used to determine bone mineralization density distribution (BMDD) as well as osteocyte lacunar density. The BMDD of type V OI bone was distinctly shifted towards higher degree of mineralization. The most frequently occurring calcium concentration (CaPeak) in cortical (Ct) and cancellous (Cn) bone was markedly increased (+11.5%, +10.4%, respectively, P<0.0001) compared to healthy reference values. Treatment with pamidronate resulted in only a slight enhancement of mineralization. The osteocyte lacunar density derived from sectioned bone area was elevated in OI type V Ct and Cn bone (+171%, P<0.0001 and +183.3%, P<0.01, respectively) versus controls. The high osteocyte density was associated with an overall immature primary bone structure (”mesh-like”) as visualized by polarized light microscopy. In summary the bone material from OI type V patients is hypermineralized, similarly to other forms of OI. The elevated osteocyte lacunar density in connection with lack of regular bone lamellation points to an exuberant primary bone formation and an alteration of the bone remodeling process in OI type V.

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“…OI Type V is an autosomal dominant form of OI, caused by pathogenic variants in IFITM5 (MIM #610967). This form of OI is characterized by interosseous membrane calcification and hyperplastic callus formation (Brizola et al, ). The prevalence of HL in this type of OI is unknown.…”

Section: Discussionmentioning

confidence: 99%

“…This form of OI is characterized by interosseous membrane calcification and hyperplastic callus formation (Brizola et al, 2015). The prevalence of HL in this type of OI is unknown.…”

Section: Hl In Individuals With Other Types Of Oimentioning

confidence: 99%

Hearing loss in individuals with osteogenesis imperfecta in North America: Results from a multicenter study

Machol

Hadley

Schmidt

et al. 2019

American J of Med Genetics Pt A

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Hearing loss (HL) is an extra‐skeletal manifestation of the connective tissue disorder osteogenesis imperfecta (OI). Systematic evaluation of the prevalence and characteristics of HL in COL1A1/COL1A2‐related OI will contribute to a better clinical management of individuals with OI. We collected and analyzed pure‐tone audiometry data from 312 individuals with OI who were enrolled in the Linked Clinical Research Centers and the Brittle Bone Disorders Consortium. The prevalence, type, and severity of HL in COL1A1/COL1A2‐related OI are reported. We show that the prevalence of HL in OI is 28% and increased with age in Type I OI but not in Types III and IV. Individuals with OI Types III and IV are at a higher risk to develop HL in the first decade of life when compared to OI Type I. We also show that the prevalence of SNHL is higher in females with OI compared to males. This study reveals new insights regarding prevalence of HL in OI including a lower general prevalence of HL in COL1A1/COL1A2‐related OI than previously reported (28.3 vs. 65%) and high prevalence of SNHL in females. Our data support the need in early routine hearing evaluation in all types of OI that can be adjusted to the severity of the skeletal disease.

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Clinical and Molecular Characterization of Osteogenesis Imperfecta Type V

Cited by 24 publications

References 26 publications

Dental and facial characteristics of osteogenesis imperfecta type V

Dental and facial characteristics of osteogenesis imperfecta type V

Hypermineralization and High Osteocyte Lacunar Density in Osteogenesis Imperfecta Type V Bone Indicate Exuberant Primary Bone Formation

Hearing loss in individuals with osteogenesis imperfecta in North America: Results from a multicenter study

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