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. 2019 Jun 12:10:375.
doi: 10.3389/fendo.2019.00375. eCollection 2019.

Expanding the Clinical Spectrum of Osteogenesis Imperfecta Type V: 13 Additional Patients and Review

Affiliations

Expanding the Clinical Spectrum of Osteogenesis Imperfecta Type V: 13 Additional Patients and Review

Yang-Jia Cao et al. Front Endocrinol (Lausanne). .

Abstract

Osteogenesis imperfecta (OI) is an inherited connective tissue disorder characterized by bone fragility and is characterized by clinical and genetic heterogeneity. Previous studies showed that the same mutation (c.-14C> T) of the IFITM5 gene is responsible for autosomal dominant OI type V. However, the mutation has a variable expressivity. Clinical heterogeneity has been recognized in OI type V. In this study, we investigated 13 individuals with molecularly confirmed OI type V from seven Chinese families and explored the genotype-phenotype relationship. Increased callus formation is not observed in all individuals, and several novel clinical features were described: joint contractures (three individuals) and unexplained hip arthritis (six individuals). Significant clinical variability was observed even within families. Specific facial features were observed in six individuals from two families consistent with the facial features associated with OI type V reported so far in the literature. Interestingly, we report the process of hypertrophic callus formation in detail for the first time, and in five individuals with hyperplastic callus, increased erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (C-RP) were measured, suggestive of inflammatory activation.

Keywords: IFITM5; mutation; osteogenesis imperfecta type V; phenotype; variability.

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Figures

Figure 1
Figure 1
Pedigrees of the individuals described; *DNA available; The black figures represent the individuals who tested positive for the IFITM5 mutation.
Figure 2
Figure 2
The identical heterozygous c.−14C > T mutation (black arrow) of IFITM5 in all the affected patients with OI type V detected by Sanger sequencing. (This figure is the sequence result for F3II1).
Figure 3
Figure 3
Clinical characteristics of OI type V caused by the IFITM5 c.−14 C> T mutation. (A–C) Phenotypic diversity within individuals, and the characteristic facial features: wide set eyes, flat nose, thin lips, broad jaw, and short, wide forehead (F6IV2, F4III6, F4III9). (D) Hyperplastic callus (F3II1). (E) Dentinogenesis imperfecta (F7II1). (F) Large olecranon and coronoid process (F6IV2). (G) Saber-like deformity of lower limbs (F4III6). (H,I) Joint contracture involving knees and toes (F4IV2, F4III9). Written informed consent for the publication of these images were obtained.
Figure 4
Figure 4
Radiological features of patients in the study. (A) Hyperplastic callus (F3II1). (B) Severe scoliosis and thin and wavy ribs (F4III9). (C) Hip arthritis with effusion and articular surface roughness (F4IV2). (D) Ossification of interosseous membrane between the radius and ulna (F2II1). (E) Radial head dislocation (F1II1). (F) Dense metaphyseal band (F2II1). Written informed consent for the publication of these images was obtained.
Figure 5
Figure 5
(A–F) Lateral X-rays of the left femur captured 15, 30, 45, 60, 75, and 90 days after fractures. Calluses occurred at the fracture site and increased over time (F3II1). Written informed consent for the publication of this image was obtained.

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