QRICH1 variants in Ververi‐Brady syndrome—delineation of the genotypic and phenotypic spectrum. Issue 1 (10th November 2020)

• Record Type: Journal Article
• Authors: Föhrenbach, Melanie; Jamra, Rami Abou; Borkhardt, Arndt; Brozou, Triantafyllia; Muschke, Petra; Popp, Bernt; Rey, Linda K.; Schaper, Jörg; Surowy, Harald; Zenker, Martin; Zweier, Christiane; Wieczorek, Dagmar; Redler, Silke
• Is Part Of: Clinical genetics. Volume 99:Issue 1(2021)
• Page Start: 199
• Page End: 207
• Publication Date: 2020-11-10
• Subjects: autism spectrum disorder -- language development disorders -- QRICH1 -- Ververi‐Brady syndrome; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.13853
• Languages: English
• ISSNs: 0009-9163

Abstract

Abstract: Ververi‐Brady syndrome (VBS, # 617982) is a rare developmental disorder, and loss‐of‐function variants in QRICH1 were implicated in its etiology. Furthermore, a recognizable phenotype was proposed comprising delayed speech, learning difficulties and dysmorphic signs. Here, we present four unrelated individuals with one known nonsense variant (c.1954C > T; p.[Arg652*]) and three novel de novo QRICH1 variants, respectively. These included two frameshift mutations (c.832_833del; p.(Ser278Leufs*25), c.1812_1813delTG; p.(Glu605Glyfs*25)) and interestingly one missense mutation (c.2207G > A; p.[Ser736Asn]), expanding the mutational spectrum. Enlargement of the cohort by these four individuals contributes to the delineation of the VBS phenotype and suggests expressive speech delay, moderate motor delay, learning difficulties/mild ID, mild microcephaly, short stature and notable social behavior deficits as clinical hallmarks. In addition, one patient presented with nephroblastoma. The possible involvement of QRICH1 in pediatric cancer assumes careful surveillance a key priority for outcome of these patients. Further research and enlargement of cohorts are warranted to learn about the genetic architecture and the phenotypic spectrum in more detail. Abstract : The Ververi‐Brady syndrome is a rare developmental disorder with a lot of hallmarks that are rather unspecific. We tried to further delineate the symptoms in this this study. Speech delay and notable social behaviour deficits seem to be the key symptoms. Our patients, as well as those described in the literature, all show mutations in the QRICH1 gene. We found three new variants that have not yet been described as well as one that has already been identified.