Exome survey of individuals affected by VATER/VACTERL with renal phenotypes identifies phenocopies and novel candidate genes.

Autor: Kolvenbach CM; Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Department of Pediatrics, University Hospital Bonn, Bonn, Germany., van der Ven AT; Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Kause F; Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Department of Pediatrics, University Hospital Bonn, Bonn, Germany., Shril S; Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Scala M; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.; Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannia Gaslini, University of Genoa, Genoa, Italy., Connaughton DM; Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Mann N; Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Nakayama M; Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Dai R; Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Kitzler TM; Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Schneider R; Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Schierbaum L; Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Department of Pediatrics, University Hospital Bonn, Bonn, Germany., Schneider S; Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Department of Pediatrics, University Hospital Bonn, Bonn, Germany., Accogli A; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy., Torella A; Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy.; Telethon Institute of Genetics and Medicine, Pozzuoli, Italy., Piatelli G; Department of Neurosurgery, Gaslini Children's Hospital, Genoa, Italy., Nigro V; Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy.; Telethon Institute of Genetics and Medicine, Pozzuoli, Italy., Capra V; Medical Genetics Unit, IRCCS Gianna Gaslini Institute, Genoa, Italy., Hoppe B; Kindernierenzentrum Bonn, Bonn, Germany., Märzheuser S; Department of Pediatric Surgery, Campus Virchow Clinic, Charité University Hospital Berlin, Berlin, Germany., Schmiedeke E; Department of Pediatric Surgery and Urology, Center for Child and Youth Health, Klinikum Bremen-Mitte, Bremen, Germany., Rehm HL; Program in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA., Mane S; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.; Yale Center for Mendelian Genomics, Yale University School of Medicine, New Haven, Connecticut, USA., Lifton RP; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.; Yale Center for Mendelian Genomics, Yale University School of Medicine, New Haven, Connecticut, USA., Dworschak GC; Department of Pediatrics, University Hospital Bonn, Bonn, Germany.; Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany., Hilger AC; Department of Pediatrics, University Hospital Bonn, Bonn, Germany.; Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany., Reutter H; Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany.; Department of Neonatology and Pediatric Intensive Care, University Hospital Bonn, Bonn, Germany.; Department of Neonatology and Pediatric Intensive Care, University Hospital Erlangen, Erlangen, Germany., Hildebrandt F; Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2021 Dec; Vol. 185 (12), pp. 3784-3792. Date of Electronic Publication: 2021 Aug 02.
DOI: 10.1002/ajmg.a.62447
Abstrakt: The acronym VATER/VACTERL refers to the rare nonrandom association of the following component features (CFs): vertebral defects (V), anorectal malformations (ARM) (A), cardiac anomalies (C), tracheoesophageal fistula with or without esophageal atresia (TE), renal malformations (R), and limb anomalies (L). For the clinical diagnosis, the presence of at least three CFs is required, individuals presenting with only two CFs have been categorized as VATER/VACTERL-like. The majority of VATER/VACTERL individuals displays a renal phenotype. Hitherto, variants in FGF8, FOXF1, HOXD13, LPP, TRAP1, PTEN, and ZIC3 have been associated with the VATER/VACTERL association; however, large-scale re-sequencing could only confirm TRAP1 and ZIC3 as VATER/VACTERL disease genes, both associated with a renal phenotype. In this study, we performed exome sequencing in 21 individuals and their families with a renal VATER/VACTERL or VATER/VACTERL-like phenotype to identify potentially novel genetic causes. Exome analysis identified biallelic and X-chromosomal hemizygous potentially pathogenic variants in six individuals (29%) in B9D1, FREM1, ZNF157, SP8, ACOT9, and TTLL11, respectively. The online tool GeneMatcher revealed another individual with a variant in ZNF157. Our study suggests six biallelic and X-chromosomal hemizygous VATER/VACTERL disease genes implicating all six genes in the expression of human renal malformations.
(© 2021 Wiley Periodicals LLC.)
Databáze: MEDLINE
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