Identification of causative variants in TXNL4A in Burn-McKeown syndrome and isolated choanal atresia.

Autor: Goos JAC; Department of Plastic and Reconstructive Surgery and Hand Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Swagemakers SMA; Department of Bioinformatics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Twigg SRF; Clinical Genetics Group, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK., van Dooren MF; Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Hoogeboom AJM; Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Beetz C; Department of Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Jena, Germany., Günther S; Department of Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Jena, Germany., Magielsen FJ; Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Ockeloen CW; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., A Ramos-Arroyo M; Department of Medical Genetics, Complejo Hospitalario de Navarra, IdiSNA, Navarra Institute for Health Research, Pamplona, Navarra, Spain., Pfundt R; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., Yntema HG; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., van der Spek PJ; Clinical Genetics Group, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK., Stanier P; Genetics and Genomic Medicine, UCL Institute of Child Health, London, UK., Wieczorek D; Institute of Human Genetics, Heinrich-Heine-University, Medical Faculty, Düsseldorf, Germany., Wilkie AOM; Clinical Genetics Group, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK., van den Ouweland AMW; Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Mathijssen IMJ; Department of Plastic and Reconstructive Surgery and Hand Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Hurst JA; Clinical Genetics Department, NE Thames Genetics Service, Great Ormond Street Hospital, London, UK.
Jazyk: angličtina
Zdroj: European journal of human genetics : EJHG [Eur J Hum Genet] 2017 Oct; Vol. 25 (10), pp. 1126-1133. Date of Electronic Publication: 2017 Jul 26.
DOI: 10.1038/ejhg.2017.107
Abstrakt: Burn-McKeown syndrome (BMKS) is a rare syndrome characterized by choanal atresia, prominent ears, abnormalities of the outer third of the lower eyelid, structural cardiac abnormalities, conductive and sensorineural hearing loss, and cleft lip. Recently, causative compound heterozygous variants were identified in TXNL4A. We analyzed an individual with clinical features of BMKS and her parents by whole-genome sequencing and identified compound heterozygous variants in TXNL4A (a novel splice site variant (c.258-2A>G, (p.?)) and a 34 bp promoter deletion (hg19 chr18:g.77748581_77748614del (type 1Δ) in the proband). Subsequently, we tested a cohort of 19 individuals with (mild) features of BMKS and 17 individuals with isolated choanal atresia for causative variants in TXNL4A by dideoxy-sequence analysis. In one individual with BMKS unrelated to the first family, we identified the identical compound heterozygous variants. In an individual with isolated choanal atresia, we found homozygosity for the same type 1Δ promoter deletion, whilst in two cousins from a family with choanal atresia and other minor anomalies we found homozygosity for a different deletion within the promoter (hg19 chr18: g.77748604_77748637del (type 2Δ)). Hence, we identified causative recessive variants in TXNL4A in two individuals with BMKS as well as in three individuals (from two families) with isolated choanal atresia.
Databáze: MEDLINE
Externí odkaz: