Weill‐Marchesani syndrome in mother and son

Young, Ian; Fielder, A R; Casey, Thomas A.

doi:10.1111/j.1399-0004.1986.tb01914.x

Cited by 14 publications

(5 citation statements)

References 11 publications

(10 reference statements)

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“…Patients born to consanguineous Lebanese parents presented with short stature, brachydactyly, limitation of joints movements, microspherophakia with luxated lenses, myopia, glaucoma, and heart malformations (Table 1), all abnormalities consistent with WMS. The absence of glaucoma, lens ectopia, microspherophakia and stiffness in the parents does not favor dominant inheritance as already reported in other families [1–5]. The mode of inheritance is autosomal‐recessive, and the brachymorphic phenotype of the parents is consistent with the expression of the gene in the heterozygotic state, as already suggested [11,12].…”

Section: Discussionsupporting

confidence: 77%

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Exclusion of chromosome 15q21.1 in autosomal‐recessive Weill–Marchesani syndrome in an inbred Lebanese family

et al. 2000

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We report an inbred family where 3 siblings had short stature, brachydactyly, limitation of joint movements, microspherophakia, luxated lenses, glaucoma, and heart malformations. Parents of the affected siblings were relatively short, but did not have any of the other features present in their siblings. Those clinical features are consistent with the Weill Marchesani syndrome (MIM 277600). Both autosomal-recessive and autosomal-dominant pedigrees have been reported, with a possible linkage to chromosome 15q21.1 in the latter. Linkage analysis at 15q21.1 in this Lebanese family allowed us to exclude the role of this region in the etiology of the syndrome. Speculations regarding the pathogenesis of the disorder are discussed.

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Section: Discussionsupporting

confidence: 77%

“…Autosomal‐recessive inheritance with partial expression in heterozygous is the most possible mode of transmission. However, dominant pedigrees have also been reported in the literature [1–5]. Lately, Wirtz et al [6] reported possible linkage to 15q21.1 in 2 families with a dominant form.…”

mentioning

confidence: 99%

Exclusion of chromosome 15q21.1 in autosomal‐recessive Weill–Marchesani syndrome in an inbred Lebanese family

et al. 2000

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“…WMS patients are observed to be of a muscular build or hypermuscular ( 31 , 32 ) but it is not known if their increased muscle mass results in increased strength or muscle function. We found that in skeletal muscle ADAMTS10 was localized to the muscle niche and its disruption perturbed ZO-1-rich tight junctions.…”

Section: Discussionmentioning

confidence: 99%

ADAMTS10-mediated tissue disruption in Weill–Marchesani syndrome

Mularczyk

Singh

Godwin

et al. 2018

Human Molecular Genetics

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Fibrillin microfibrils are extracellular matrix assemblies that form the template for elastic fibres, endow blood vessels, skin and other elastic tissues with extensible properties. They also regulate the bioavailability of potent growth factors of the TGF-β superfamily. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)10 is an essential factor in fibrillin microfibril function. Mutations in fibrillin-1 or ADAMTS10 cause Weill–Marchesani syndrome (WMS) characterized by short stature, eye defects, hypermuscularity and thickened skin. Despite its importance, there is poor understanding of the role of ADAMTS10 and its function in fibrillin microfibril assembly. We have generated an ADAMTS10 WMS mouse model using Clustered Regularly Spaced Interspaced Short Palindromic Repeats and CRISPR associated protein 9 (CRISPR-Cas9) to introduce a truncation mutation seen in WMS patients. Homozygous WMS mice are smaller and have shorter long bones with perturbation to the zones of the developing growth plate and changes in cell proliferation. Furthermore, there are abnormalities in the ciliary apparatus of the eye with decreased ciliary processes and abundant fibrillin-2 microfibrils suggesting perturbation of a developmental expression switch. WMS mice have increased skeletal muscle mass and more myofibres, which is likely a consequence of an altered skeletal myogenesis. These results correlated with expression data showing down regulation of Growth differentiation factor (GDF8) and Bone Morphogenetic Protein (BMP) growth factor genes. In addition, the mitochondria in skeletal muscle are larger with irregular shape coupled with increased phospho-p38 mitogen-activated protein kinase (MAPK) suggesting muscle remodelling. Our data indicate that decreased SMAD1/5/8 and increased p38/MAPK signalling are associated with ADAMTS10-induced WMS. This model will allow further studies of the disease mechanism to facilitate the development of therapeutic interventions.

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“…1,[3][4][5][6] Both autosomal-recessive (AR) and autosomal-dominant (AD) forms of the disease have been described. [7][8][9][10] Three mutations in ADAMTS10 (MIM *608990, ADAM metallopeptidase with thrombospondin type 1 motif, 10) were reported in two Middle Eastern families with an AR form of the disease and in a single sporadic case of WMS. These include a nonsense mutation (p.R237X) and two splice mutations (810þ1 G > A and 1190þ1 G > A).…”

Section: Introductionmentioning

confidence: 99%

Homozygous Mutations in ADAMTS10 and ADAMTS17 Cause Lenticular Myopia, Ectopia Lentis, Glaucoma, Spherophakia, and Short Stature

Morales

Al-Sharif

Khalil

et al. 2009

The American Journal of Human Genetics

209

187

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Weill-Marchesani syndrome (WMS) is a well-characterized disorder in which patients develop eye and skeletal abnormalities. Autosomal-recessive and autosomal-dominant forms of WMS are caused by mutations in ADAMTS10 and FBN1 genes, respectively. Here we report on 13 patients from seven unrelated families from the Arabian Peninsula. These patients have a constellation of features that fall within the WMS spectrum and follow an autosomal-recessive mode of inheritance. Individuals who came from two families and met the diagnostic criteria for WMS were each found to have a different homozygous missense mutation in ADAMTS10. Linkage analysis and direct sequencing of candidate genes in another two families and a sporadic case with phenotypes best described as WMS-like led to the identification of three homozygous mutations in the closely related ADAMTS17 gene. Our clinical and genetic findings suggest that ADAMTS17 plays a role in crystalline lens zonules and connective tissue formation and that mutations in ADAMTS17 are sufficient to produce some of the main features typically described in WMS.

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Weill‐Marchesani syndrome in mother and son

Abstract: A mother and son, each showing the characteristic features of the Weill‐Marchesani syndrome, are described. It is suggested that this family provides further evidence for genetic heterogeneity in this condition.

Cited by 14 publications

References 11 publications

Exclusion of chromosome 15q21.1 in autosomal‐recessive Weill–Marchesani syndrome in an inbred Lebanese family

Exclusion of chromosome 15q21.1 in autosomal‐recessive Weill–Marchesani syndrome in an inbred Lebanese family

ADAMTS10-mediated tissue disruption in Weill–Marchesani syndrome

Homozygous Mutations in ADAMTS10 and ADAMTS17 Cause Lenticular Myopia, Ectopia Lentis, Glaucoma, Spherophakia, and Short Stature

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