Patients with geleophysic dysplasia are not always geleophysic

Santolaya, Jose M.; Groninga, Lori C.; Delgado, Alfonso; Monasterio, Jose L.; Camarero, Carmen; Bilbao, Francisco José Larrea

doi:10.1002/(sici)1096-8628(19971003)72:1<85::aid-ajmg18>3.0.co;2-q

Cited by 17 publications

(7 citation statements)

References 12 publications

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“…Both the intra-lumenal and epithelial vesicles stained strongly with periodic acid Schiff (PAS) stain ( Fig. 3 B), consistent with the previously documented appearance of GD tracheal, liver and cardiac biopsies, which had shown carbohydrate-enriched inclusions in these organs, and led to designation of GD as a glycoprotein storage disorder ( Spranger et al, 1984 ; Shohat et al, 1990 ; Santolaya et al, 1997 ). We found that this PAS-positive material was sensitive to α-amylase digestion, indicative of substantial glycogen content ( Fig.…”

Section: Resultssupporting

confidence: 85%

Adamtsl2 deletion results in bronchial fibrillin microfibril accumulation and bronchial epithelial dysplasia – a novel mouse model providing insights into geleophysic dysplasia

Hubmacher

Wang

Mecham

et al. 2015

Disease Models &Amp; Mechanisms

113

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Mutations in the secreted glycoprotein ADAMTSL2 cause recessive geleophysic dysplasia (GD) in humans and Musladin–Lueke syndrome (MLS) in dogs. GD is a severe, often lethal, condition presenting with short stature, brachydactyly, stiff skin, joint contractures, tracheal-bronchial stenosis and cardiac valve anomalies, whereas MLS is non-lethal and characterized by short stature and severe skin fibrosis. Although most mutations in fibrillin-1 (FBN1) cause Marfan syndrome (MFS), a microfibril disorder leading to transforming growth factor-β (TGFβ) dysregulation, domain-specific FBN1 mutations result in dominant GD. ADAMTSL2 has been previously shown to bind FBN1 and latent TGFβ-binding protein-1 (LTBP1). Here, we investigated mice with targeted Adamtsl2 inactivation as a new model for GD (Adamtsl2−/− mice). An intragenic lacZ reporter in these mice showed that ADAMTSL2 was produced exclusively by bronchial smooth muscle cells during embryonic lung development. Adamtsl2−/− mice, which died at birth, had severe bronchial epithelial dysplasia with abnormal glycogen-rich inclusions in bronchial epithelium resembling the cellular anomalies described previously in GD. An increase in microfibrils in the bronchial wall was associated with increased FBN2 and microfibril-associated glycoprotein-1 (MAGP1) staining, whereas LTBP1 staining was increased in bronchial epithelium. ADAMTSL2 was shown to bind directly to FBN2 with an affinity comparable to FBN1. The observed extracellular matrix (ECM) alterations were associated with increased bronchial epithelial TGFβ signaling at 17.5 days of gestation; however, treatment with TGFβ-neutralizing antibody did not correct the epithelial dysplasia. These investigations reveal a new function of ADAMTSL2 in modulating microfibril formation, and a previously unsuspected association with FBN2. Our studies suggest that the bronchial epithelial dysplasia accompanying microfibril dysregulation in Adamtsl2−/− mice cannot be reversed by TGFβ neutralization, and thus might be mediated by other mechanisms.

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Section: Resultssupporting

confidence: 85%

Adamtsl2 deletion results in bronchial fibrillin microfibril accumulation and bronchial epithelial dysplasia – a novel mouse model providing insights into geleophysic dysplasia

Hubmacher

Wang

Mecham

et al. 2015

Disease Models &Amp; Mechanisms

113

View full text Add to dashboard Cite

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“…Although the syndrome obtains its name because of the typical facies (gelios: happy, physis: nature), Santolata et al emphasised that some published cases do not have this appearance. 8 Although the underlying metabolic or genetic basis is unknown, some authors have argued that there are similarities between GD and the lysosomal storage disease, mucopolysaccharidosis, such as the coarse facial features, short stature and skeletal changes including progressive limitation of joint movement, thickened skin and microscopic changes resembling lysosome storage disorders of these tissues. 5 Conditions that might be confused with GD are: acromicric dysplasia, characterised by severe growth retardation, markedly short hands and feet and a short nose, and Moore-Federman syndrome, characterised by short limb dwarfism, stiff joints, thick skin and ocular findings such as glaucoma, cataract and retinal detachment.…”

Section: Discussionmentioning

confidence: 99%

“…Eosinophils with abnormally coarse granulation have been reported. 8 Although most patients die in the 1st 6 years of life owing to the progressive involvement of heart valves and myocardium and, sometimes, stenosis of the upper respiratory tract, milder cases have been reported. 2,9,10 …”

Section: Discussionmentioning

confidence: 99%

Clinical and morphological phenotype of geleophysic dysplasia

Giray

Kýr

Bora

et al. 2008

Annals of Tropical Paediatrics

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Geleophysic dysplasia (GD) is a rare, recessively inherited lysosomal storage disorder of unknown origin with a progressive course. A 9-year-old Turkish boy born to consanguineous parents with findings typical of GD is reported. Cardiac abnormalities included mitral and aortic stenosis with aortic insufficiency. There was persistent hypo-uricacidaemia, severe pulmonary hypertension and tricuspid insufficiency. He required aortic and mitral valve replacement but, unfortunately, died of a severe pulmonary infection in the post-operative period. The condition has to be differentiated from lysosomal storage disorders such as mucopolysaccharidosis.

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“…First, thickened skin and hepatomegaly are features of both geleophysic dysplasia and Moore-Federman syndrome, but are never observed in acromicric dysplasia. Second, cardiac valve dysplasia is observed in geleophysic dysplasia only 5. Third, while life expectancy and functional prognosis are good in acromicric dysplasia and Moore-Federman syndrome, they are poor in geleophysic dysplasia 6.…”

Section: Discussionmentioning

confidence: 99%

Acromicric dysplasia: long term outcome and evidence of autosomal dominant inheritance

Faivre

Merrer²,

Baumann³

et al. 2001

Journal of Medical Genetics

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Acromicric dysplasia is a rare bone dysplasia characterised by short stature, short hands and feet, normal intelligence, mild facial dysmorphism, and characteristic x ray abnormalities of the hands. Only a very small number of children with this condition have been reported so far. Here we report on a series of 22 patients including 10 boys and 12 girls with acromicric dysplasia. Length was normal at birth and height fell progressively oV the centiles postnatally. The mean adult height was 130 cm (133 cm in males, 129 cm in females). The hands, feet, and limbs were short and OFC was normal. Intelligence was normal and mild dysmorphic features were noted. Other occasional features included well developed muscles, a hoarse voice, generalised joint limitation in some patients, frequent ear, tracheal, and respiratory complication, and spine abnormalities. Long term follow up showed that facial dysmorphism was less obvious in adults and that carpal tunnel syndrome was frequent in older patients. Apart from short metacarpals and phalanges, internal notch of the second metacarpal, external notch of the fifth metacarpal, and internal notch of the femoral heads, there were no major x ray abnormalities. No major complications, such as cardiac disease or major orthopaedic problems, occurred in the course of the disease. The condition appeared to be sporadic in 16 cases but the observation of vertical transmission in three families was consistent with an autosomal dominant mode of inheritance. (J Med Genet 2001;38:745-749)

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Patients with geleophysic dysplasia are not always geleophysic

Cited by 17 publications

References 12 publications

Adamtsl2 deletion results in bronchial fibrillin microfibril accumulation and bronchial epithelial dysplasia – a novel mouse model providing insights into geleophysic dysplasia

Adamtsl2 deletion results in bronchial fibrillin microfibril accumulation and bronchial epithelial dysplasia – a novel mouse model providing insights into geleophysic dysplasia

Clinical and morphological phenotype of geleophysic dysplasia

Acromicric dysplasia: long term outcome and evidence of autosomal dominant inheritance

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