title: De novo deletion of HOXB gene cluster in a patient with failure to thrive, developmental delay, gastroesophageal reflux and bronchiectasis.
abstract: We report a female patient with a complex phenotype consisting of failure to thrive, developmental delay, congenital bronchiectasis, gastroesophageal reflux and bilateral inguinal hernias. Chromosomal microarray analysis revealed a 230 kilobase deletion in chromosomal region 17q21.32 (arr[hg19] 17q21.32(46 550 362-46 784 039)×1) encompassing only 9 genes - HOXB1 to HOXB9. The deletion was not found in her mother or father. This is the first report of a patient with a HOXB gene cluster deletion involving only HOXB1 to HOXB9 genes. By comparing our case to previously reported five patients with larger chromosomal aberrations involving the HOXB gene cluster, we can suppose that HOXB gene cluster deletions are responsible for growth retardation, developmental delay, and specific facial dysmorphic features. Also, we suppose that bilateral inguinal hernias, tracheo-esophageal abnormalities, and lung malformations represent features with incomplete penetrance. Interestingly, previously published knock-out mice with targeted heterozygous deletion comparable to our patient did not show phenotypic alterations.
authors.affiliation: Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia; Institute of Biomedicine and Translational Medicine, Department of Biomedicine, University of Tartu, Tartu, Estonia. Electronic address: sander.pajusalu@kliinikum.ee.
authors.forename: Sander
authors.initials: S
authors.lastname: Pajusalu
authors.affiliation: Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia; Institute of Biomedicine and Translational Medicine, Department of Biomedicine, University of Tartu, Tartu, Estonia; Department of Paediatrics, University of Tartu, Tartu, Estonia.
authors.forename: Tiia
authors.initials: T
authors.lastname: Reimand
authors.affiliation: Department of Paediatrics, University of Tartu, Tartu, Estonia; Children's Clinic, Tartu University Hospital, Tartu, Estonia.
authors.forename: Oivi
authors.initials: O
authors.lastname: Uibo
authors.affiliation: Department of Paediatrics, University of Tartu, Tartu, Estonia; Children's Clinic, Tartu University Hospital, Tartu, Estonia.
authors.forename: Maire
authors.initials: M
authors.lastname: Vasar
authors.affiliation: Department of Paediatrics, University of Tartu, Tartu, Estonia; Children's Clinic, Tartu University Hospital, Tartu, Estonia.
authors.forename: Inga
authors.initials: I
authors.lastname: Talvik
authors.affiliation: Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia; Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Olga
authors.initials: O
authors.lastname: Zilina
authors.affiliation: Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.
authors.forename: Pille
authors.initials: P
authors.lastname: Tammur
authors.affiliation: Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia; Department of Paediatrics, University of Tartu, Tartu, Estonia.
authors.forename: Katrin
authors.initials: K
authors.lastname: Õunap
mesh_terms: D001987:Bronchiectasis / Q000175:diagnosis / Q000235:genetics*; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics*; D005183:Failure to Thrive / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005764:Gastroesophageal Reflux / Q000175:diagnosis / Q000235:genetics*; D017353:Gene Deletion; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D013577:Syndrome
chemical_list: D018398:Homeodomain Proteins
keywords: 17q21.32 deletion; Chromosomal microarray; Congenital bronchiectasis; Developmental delay; HOXB gene cluster