title: Deletion of 19q13 reveals clinical overlap with Dubowitz syndrome.
abstract: Dubowitz syndrome is a presumed autosomal recessive disorder characterized by multiple congenital abnormalities: microcephaly, learning and developmental delay, growth failure, and a predisposition to allergies and eczema. There have been more than 150 individuals reported to have this diagnosis, but no unifying genetic alteration has been identified indicating genetic heterogeneity. We report on a pair of monozygotic twins diagnosed clinically with Dubowitz syndrome by Professor Dubowitz over 30 years ago and identified to have a de novo heterozygous 3.2-Mb deletion at 19q13.11q13.12. Exome sequencing did not identify either a putative pathogenic variant on the trans allele supporting recessive inheritance or any other causative sequence variants. Comparison of the phenotype in our cases shows considerable overlap with the 19q13.11 microdeletion syndrome, suggesting that a subset of individuals diagnosed with Dubowitz syndrome may be due to deletions at 19q13. Our finding further reinforces the genetic and phenotypic heterogeneity of Dubowitz syndrome.
authors.affiliation: Manchester Centre for Genomic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester Academic Health Science Centre (MAHSC), Manchester, UK.|Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre (MAHSC), Manchester, UK.
authors.forename: Jill E
authors.initials: JE
authors.lastname: Urquhart
authors.affiliation: Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre (MAHSC), Manchester, UK.
authors.forename: Simon G
authors.initials: SG
authors.lastname: Williams
authors.affiliation: Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre (MAHSC), Manchester, UK.
authors.forename: Sanjeev S
authors.initials: SS
authors.lastname: Bhaskar
authors.affiliation: Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre (MAHSC), Manchester, UK.
authors.forename: Naomi
authors.initials: N
authors.lastname: Bowers
authors.affiliation: Manchester Centre for Genomic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester Academic Health Science Centre (MAHSC), Manchester, UK.|Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre (MAHSC), Manchester, UK.
authors.forename: Jill
authors.initials: J
authors.lastname: Clayton-Smith
authors.affiliation: Manchester Centre for Genomic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester Academic Health Science Centre (MAHSC), Manchester, UK.|Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre (MAHSC), Manchester, UK.
authors.forename: William G
authors.initials: WG
authors.lastname: Newman
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D004485:Eczema / Q000235:genetics* / Q000473:pathology; D019066:Facies; D006130:Growth Disorders / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D008297:Male; D008831:Microcephaly / Q000235:genetics* / Q000473:pathology; D017384:Sequence Deletion; D014430:Twins, Monozygotic / Q000235:genetics*