Is geroderma osteodysplastica underdiagnosed?

Hunter, Alasdair G. W.

doi:10.1136/jmg.25.12.854

Cited by 28 publications

(26 citation statements)

References 4 publications

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“…The skeletal phenotypic features observed in Gorab Prx1 tibiae are generally consistent with clinical reports on GO patients (Al-Gazali et al, 2001; Hennies et al, 2008; Hunter, 1988; Hunter et al, 1978; Lisker et al, 1979; Nanda et al, 2008; Rajab et al, 2008), who have short stature and bowed long bones (tibia and femur) and often experience bone fractures (Rajab et al, 2008). Our current results from tibial morphological measures are in agreement with previous observations of Steiner et al 2015 (Steiner et al, 2015) showing that Gorab deficiency leads to a retardation of long bone growth and a dramatic reduction in trabecular and cortical bone volumes.…”

Section: Discussionsupporting

confidence: 85%

“…Gerodermia osteodysplastica (GO, MIM#231070) is a hereditary segmental progeroid disorder (Al-Gazali et al, 2001; Hennies et al, 2008; Nanda et al, 2008; Rajab et al, 2008), one of the few monogenic disorders other than osteogenesis imperfecta that has pronounced osteoporosis and fractures already in childhood (Hunter, 1988; Lisker et al, 1979; Nanda et al, 2008). Individuals with GO also have a prematurely aged appearance with wrinkled skin and generalized connective tissue weakness (Al-Bughaili et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Examining tissue composition, whole-bone morphology and mechanical behavior of GorabPrx1 mice tibiae: A mouse model of premature aging

Yang

Albiol

Chan

et al. 2017

Journal of Biomechanics

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Gerodermia osteodysplastica (GO) is a segmental progeroid disorder caused by loss-of-function mutations in the GORAB gene, associated with early onset osteoporosis and bone fragility. A conditional mouse model of GO (GorabPrx1) was generated in which the Gorab gene was deleted in long bones. We examined the biomechanical/functional relevance of the GorabPrx1 mutants as a premature aging model by characterizing bone composition, tissue-level strains, and whole-bone morphology and mechanical properties of the tibia. MicroCT imaging showed that GorabPrx1 tibiae had an increased anterior convex curvature and decreased cortical cross-sectional area, cortical thickness and moments of inertia, compared to littermate control (LC) tibiae. Fourier transform infrared imaging (FTIRI) indicated a 34% decrease in mineral/matrix ratio and a 27% increase in acid phosphate content in the posterior metaphyseal cortex of the GorabPrx1 tibiae (p<0.05), suggesting delayed mineralization. In vivo strain gauge measurement and finite element analysis showed ~two times higher tissue-level strains within the GorabPrx1 tibiae relative to LC tibiae when subjected to axial compressive loads of the same magnitude. Three-point bending tests suggested that GorabPrx1 tibiae were weaker and more brittle, as indicated by decreasing whole-bone strength (46%), stiffness (55%), work-to-fracture (61%) and post-yield displacement (47%). Many of these morphological and biomechanical characteristics of the GorabPrx1 tibia recapitulated changes in other animal models of skeletal aging. Future studies are necessary to confirm how our observations might guide the way to a better understanding and treatment of GO.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Examining tissue composition, whole-bone morphology and mechanical behavior of GorabPrx1 mice tibiae: A mouse model of premature aging

Yang

Albiol

Chan

et al. 2017

Journal of Biomechanics

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“…Similar observations were made previously [Gazit et al, 1973;Fitzsimmons et al, 1985]. Hunter [1988] suggested that GO may be underdiagnosed, which may be also be true for WSS. We suggest considering WSS and GO in adult patients who tend to look ''older than their age'' and who have early onset osteopenia, brittle bones and scoliosis.…”

Section: Discussionsupporting

confidence: 84%

Geroderma osteodysplasticum hereditaria and wrinkly skin syndrome in 22 patients from Oman

Rajab

Kornak

Budde

et al. 2008

American J of Med Genetics Pt A

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Excessive skin wrinkling and cutis laxa are seen in many genetic conditions and overlapping features can make a clinical diagnosis difficult. Here we report on 22 Omani patients from 11 consanguineous families with the diagnosis of wrinkly skin syndrome (WSS, OMIM 278250) or geroderma osteodysplasticum hereditaria (GO, OMIM 231070). The WSS phenotype evolves during early childhood and includes a generalized and excessive skin wrinkling, dental problems, herniae, foot deformities, hip dislocations, growth retardation, and a large anterior fontanelle. The facial gestalt is characterized by a broad nasal bridge, hypertelorism, and downslanting palpebral fissures. We were unable to differentiate between WSS and cutis laxa with growth and developmental delay (CLGDD, OMIM 219200) suggesting that both can be considered as one entity. Distinct hallmarks of GO were skin wrinkling limited to the dorsum of hands and feet and to the abdomen, normal fontanelles, maxillary hypoplasia, bowed long bones, and osteopenia with frequent fractures. In contrast to the attenuation of the skin phenotype with age in WSS, adult patients with GO appeared prematurely aged. A serum sialotransferrin type 2 pattern was found in all four WSS patients tested. Apolipoprotein CIII (a marker for O-glycosylation) was normal suggesting that WSS is frequently associated with a N-protein glycosylation defect, probably at the level of processing (CDG-II). All four investigated GO patients showed normal sialotransferrin patterns. The known loci for cutis laxa and WSS on 2q31, 5q23-q31, 7q11, 11q13, and 14q32 were excluded. We suggest that WSS and GO are distinct entities with overlapping features.

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“…In this study we investigated the molecular cause of gerodermia osteodysplastica (also: geroderma osteodysplasticum, GO; OMIM 231070), a rare autosomal recessive disorder characterized by lax, wrinkled skin, joint laxity, and a typical face with a prematurely aged appearance. Skeletal signs include severe osteoporosis leading to frequent fractures, malar and mandibular hypoplasia, and a variable degree of growth retardation 1,2 . According to the current definition, GO can be regarded as a segmental progeroid disorder involving bone and skin 3 .…”

mentioning

confidence: 99%

Gerodermia osteodysplastica is caused by mutations in SCYL1BP1, a Rab-6 interacting golgin

et al. 2008

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Gerodermia osteodysplastica (GO) is an autosomal recessive disorder characterized by wrinkly skin and osteoporosis. Here we demonstrate that GO is caused by loss-of-function mutations in SCYL1BP1, which is expressed at high levels in skin and osteoblasts. The protein localizes to the Golgi apparatus and interacts with Rab6, identifying SCYL1BP1 as a novel golgin. These results associate abnormalities of the secretory pathway with age-related changes in connective tissues.

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Is geroderma osteodysplastica underdiagnosed?

Cited by 28 publications

References 4 publications

Examining tissue composition, whole-bone morphology and mechanical behavior of GorabPrx1 mice tibiae: A mouse model of premature aging

Examining tissue composition, whole-bone morphology and mechanical behavior of GorabPrx1 mice tibiae: A mouse model of premature aging

Geroderma osteodysplasticum hereditaria and wrinkly skin syndrome in 22 patients from Oman

Gerodermia osteodysplastica is caused by mutations in SCYL1BP1, a Rab-6 interacting golgin

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