De novo microduplications at 1q41, 2q37.3, and 8q24.3 in patients with VATER/VACTERL association
Alina C. Hilger,Charlotte Schramm,Tracie Pennimpede,Lars Wittler,Gabriel C. Dworschak,Enrika Bartels,Hartmut Engels,Alexander M. Zink,Franziska Degenhardt,Annette M. Müller,Eberhard Schmiedeke,Sabine Grasshoff-Derr,Stefanie Märzheuser,Stuart Hosie,Stefan Holland-Cunz,Charlotte H. W. Wijers,Carlo Marcelis,Iris A.L.M. van Rooij,Friedhelm Hildebrandt,Friedhelm Hildebrandt,Bernhard G. Herrmann,Bernhard G. Herrmann,Markus M. Nöthen,Michael Ludwig,Heiko Reutter,Heiko Reutter,Markus Draaken +26 more
TLDR
Although no disease-causing mutation was identified, mouse expression studies suggest GPR 35 to be involved in the development of the VATER/VACTERL phenotype and follow-up of GPR35 and the other genes comprising the identified duplications is warranted.Abstract:
The acronym VATER/VACTERL association describes the combination of at least three of the following congenital anomalies: vertebral defects (V), anorectal malformations (A), cardiac defects (C), tracheoesophageal fistula with or without esophageal atresia (TE), renal malformations (R), and limb defects (L). We aimed to identify highly penetrant de novo copy number variations (CNVs) that contribute to VATER/VACTERL association. Array-based molecular karyotyping was performed in a cohort of 41 patients with VATER/VACTERL association and 6 patients with VATER/VACTERL-like phenotype including all of the patients' parents. Three de novo CNVs were identified involving chromosomal regions 1q41, 2q37.3, and 8q24.3 comprising one (SPATA17), two (CAPN10, GPR35), and three (EPPK1, PLEC, PARP10) genes, respectively. Pre-existing data from the literature prompted us to choose GPR35 and EPPK1 for mouse expression studies. Based on these studies, we prioritized GPR35 for sequencing analysis in an extended cohort of 192 patients with VATER/VACTERL association and VATER/VACTERL-like phenotype. Although no disease-causing mutation was identified, our mouse expression studies suggest GPR35 to be involved in the development of the VATER/VACTERL phenotype. Follow-up of GPR35 and the other genes comprising the identified duplications is warranted.read more
Citations
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The therapeutic potential of orphan GPCRs, GPR35 and GPR55
TL;DR: Reports that suggest that GPR35/CXCR8 and GPR55 may be promising therapeutic targets, with diverse physiological roles are reviewed.
Journal ArticleDOI
Clinical and etiological heterogeneity in patients with tracheo-esophageal malformations and associated anomalies.
Erwin Brosens,Mirjam Ploeg,Yolande van Bever,Anna E Koopmans,Hanneke IJsselstijn,Robbert J. Rottier,Rene M. H. Wijnen,Dick Tibboel,Annelies de Klein +8 more
TL;DR: The phenotypical and genetic heterogeneity seen in EA/TEF patients indicates not one underlying cause, but several; unraveling the complex multifactorial and heterogeneous etiology of EA/ TEF and associated features will require large cohorts of patients.
Journal ArticleDOI
Genetic and nongenetic etiology of nonsyndromic anorectal malformations: a systematic review.
Charlotte H. W. Wijers,Iris A.L.M. van Rooij,Carlo Marcelis,Han G. Brunner,Ivo de Blaauw,Nel Roeleveld +5 more
TL;DR: In future studies, large cohorts of patients with ARM from national and international collaborations are needed to acquire new hypotheses and knowledge through hypothesis-generating approaches to conclude with unifying hypotheses and directions for future research.
Journal ArticleDOI
The genetic landscape and clinical implications of vertebral anomalies in VACTERL association
Yixin Chen,Zhenlei Liu,Jia Chen,Yuzhi Zuo,Sen Liu,Weisheng Chen,Gang Liu,Guixing Qiu,Philip F. Giampietro,Nan Wu,Zhihong Wu +10 more
TL;DR: The genetic studies of the VACTERL association, especially focusing on the genetic aetiology of patients with vertebral anomalies, are summarized and a better evidence for genetic diagnosis of the association and vertebral anomaly is provided.
Journal ArticleDOI
The emerging pharmacology and function of GPR35 in the nervous system.
TL;DR: An update on both the pharmacology and potential function of GPR35 is presented, particularly pertaining to the nervous system, as a potential effector of regulation of mechanical sensitivity and analgesia of the Ret tyrosine kinase and as a receptor involved in the transmission of anti‐inflammatory effects of aspirin through affecting leucocyte rolling, adhesion and extravasation.
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The VATER association. Vertebral defects, Anal atresia, T-E fistula with esophageal atresia, Radial and Renal dysplasia: a spectrum of associated defects.
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TL;DR: The VATER association is a group of congenital anomalies with a nonrandom tendency for concurrence that includes vertebral, vascular, anorectal malformation, tracheoesophageal fistula with esophagesia, radial-limb, and renal abnormalities.
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Targeted inactivation of plectin reveals essential function in maintaining the integrity of skin, muscle, and heart cytoarchitecture
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TL;DR: Plectin (-/-) mice will provide a useful tool for the study of EBS-MD, and possibly other types of plectin-related myopathies involving skeletal and cardiac muscle, in an organism amenable to genetic manipulation.
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