Mutations in SH3PXD2B cause Borrone dermato-cardio-skeletal syndrome

Wilson, Gregory V.; Sunley, Jasmine; Smith, Katherine R.; Pope, Kate; Bromhead, Catherine J; Fitzpatrick, Elizabeth; Rocco, Maja Di; Steensel, M.A.M. van; Coman, David; Leventer, Richard J.; Delatycki, Martin B.; Amor, David J.; Bahlo, Melanie; Lockhart, Paul J.

doi:10.1038/ejhg.2013.229

Cited by 32 publications

(38 citation statements)

References 23 publications

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“…However, we did not identify deleterious changes of SH3PXD2B or its homolog SH3PXD2A . Rather, we found a novel homozygous missense MMP14 mutation in these patients (Wilson et al, ). We recently reported that it mostly likely represents a hypomorphic allele (De Vos et al, ).…”

Section: Introductionmentioning

confidence: 53%

“…Borrone, Di Rocco, Crovato, Camera, & Gambini () described two brothers with similar features. In these two patients, as well as in individuals previously diagnosed with FTHS, we identified homozygous mutations in SH3PXD2B (MIM #613293; Wilson et al, ).…”

Section: Introductionmentioning

confidence: 79%

“…Most examined individuals with an SH3PXD2B or MMP14 mutation had a broad mouth, as well as one third of examined patients with an MMP2 mutation. Finally, thick lips and either a small or heavy mandible have been reported in most examined patients with an SH3PXD2B , MMP14 , or MMP2 mutation (Al Aqeel et al, ; Al Kaissi et al, ; Azzollini et al, ; Bader‐Meunier et al, ; Bendon et al, ; Bhavani et al, ; Borrone et al, ; Castberg et al, ; Chang et al, ; Eisenstein et al, ; Ekbote et al, ; Gok et al, ; Hamel et al, ; Iqbal et al, ; Jeong et al, ; Maas et al, ; Martignetti et al, ; Mégarbané et al, ; Phadke & Dalal, ; Pichler et al, ; Prapanpoch et al, ; Rouzier et al, ; Temtamy et al, ; Ter Haar et al, ; Tuysuz et al, ; Vanatka et al, ; Van Steensel et al, ; Wilson et al, ; Winchester et al, ; Zankl et al, ; Zankl et al, ; Zrhidri et al, ).…”

Section: Discussion and Reviewmentioning

confidence: 99%

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Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling

Vos

Wong

Welting

et al. 2019

American J of Med Genetics Pt A

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Frank-Ter Haar syndrome (FTHS), Winchester syndrome (WS), and multicentric osteolysis, nodulosis, and arthropathy (MONA) are ultra-rare multisystem disorders characterized by craniofacial malformations, reduced bone density, skeletal and cardiac anomalies, and dermal fibrosis. These autosomal recessive syndromes are caused by homozygous mutation or deletion of respectively SH3PXD2B (SH3 and PX Domains 2B), MMP14 (matrix metalloproteinase 14), or MMP2. Here, we give an overview of the clinical features of 63 previously reported patients with an SH3PXD2B, MMP14, or MMP2 mutation, demonstrating considerable clinical overlap between FTHS, WS, and MONA. Interestingly, the protein products of SH3PXD2B, MMP14, and MMP2 directly cooperate in collagen remodeling. We review animal models for these three disorders that accurately reflect the major clinical features and likewise show significant phenotypical similarity with each other. Furthermore, they demonstrate that defective collagen remodeling is central in the underlying pathology. As such, we propose a nosological revision, placing these SH3PXD2B, MMP14, and MMP2 related syndromes in a novel "defective collagenremodelling spectrum (DECORS)". In our opinion, this revised nosology better reflects the central role for impaired collagen remodeling, a potential target for pharmaceutical intervention. K E Y W O R D SECM remodeling, MMP14, MMP2, podosomes, SH3PXD2B

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Section: Introductionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 79%

Section: Discussion and Reviewmentioning

confidence: 99%

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Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling

Vos

Wong

Welting

et al. 2019

American J of Med Genetics Pt A

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“…Adult patients with this syndrome have been characterized as having acne conglobata with hypertrophic scarring and thickened skin . FTHS is inherited as an autosomal recessive trait and is caused by loss‐of‐function mutations and deletions in SH3PXD2B on chromosome 5q35·1 . SH3PXD2B codes for TKS4, a tyrosine kinase substrate adaptor protein required for podosome maturation.…”

Section: Human Monogenic Disorders That Cause Acnementioning

confidence: 99%

“…68 FTHS is inherited as an autosomal recessive trait and is caused by loss-of-function mutations and deletions in SH3PXD2B on chromosome 5q35Á1. [69][70][71][72] SH3PXD2B codes for TKS4, a tyrosine kinase substrate adaptor protein required for podosome maturation.…”

Section: Frank-ter Haar Syndrome (Mim 249420)mentioning

confidence: 99%

What does acne genetics teach us about disease pathogenesis?

2019

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Summary Background Acne vulgaris is a highly prevalent inflammatory skin disorder with a complex pathogenesis, characterized by comedones, papules, pustules and nodules. Familial preponderance clearly indicates a genetic basis for acne vulgaris, but until recently solid genetic associations were lacking. Results The advent of high‐resolution genotyping array technologies has allowed for large‐scale studies with both family‐based and cross‐sectional designs. These studies have revealed genetic loci encompassing genes that could be active in biological pathways and processes underlying acne vulgaris. However, specific functional consequences of those variants remain elusive. In parallel, investigations into rare disorders and syndromes that incorporate features of acne or acne‐like lesions have recently accelerated our understanding of disease pathogenesis. The genes revealed by these rare disorders highlight mechanisms cardinal for pilosebaceous biology and therefore anchor our insights from genetic association studies for acne vulgaris. Conclusions The next phase of research will require more in‐depth mechanistic investigations of loci and genes implicated in acne phenotypes to define the key molecular players driving the disorder. Concurrently, new treatments for acne vulgaris could be developed by dissecting the candidate molecular pathways to identify druggable targets.

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Closing the Gap: Genetic and Genomic Continuum from Syndromic to Nonsyndromic Craniosynostoses

et al. 2014

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Craniosynostosis, a condition that includes the premature fusion of one or multiple cranial sutures, is a relatively common birth defect in humans and the second most common craniofacial anomaly after orofacial clefts. There is a significant clinical variation among different sutural synostoses as well as significant variation within any given single-suture synostosis. Craniosynostosis can be isolated (i.e., nonsyndromic) or occurs as part of a genetic syndrome (e.g., Crouzon, Pfeiffer, Apert, Muenke, and Saethre-Chotzen syndromes). Approximately 85 % of all cases of craniosynostosis are nonsyndromic. Several recent genomic discoveries are elucidating the genetic basis for nonsyndromic cases and implicate the newly identified genes in signaling pathways previously found in syndromic craniosynostosis. Published epidemiologic and phenotypic studies clearly demonstrate that nonsyndromic craniosynostosis is a complex and heterogeneous condition supporting a strong genetic component accompanied by environmental factors that contribute to the pathogenetic network of this birth defect. Large population, rather than single-clinic or hospital-based studies is required with phenotypically homogeneous subsets of patients to further understand the complex genetic, maternal, environmental, and stochastic factors contributing to nonsyndromic craniosynostosis. Learning about these variables is a key in formulating the basis of multidisciplinary and lifelong care for patients with these conditions.

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Mutations in SH3PXD2B cause Borrone dermato-cardio-skeletal syndrome

Cited by 32 publications

References 23 publications

Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling

Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling

What does acne genetics teach us about disease pathogenesis?

Closing the Gap: Genetic and Genomic Continuum from Syndromic to Nonsyndromic Craniosynostoses

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