title: HOXA genes cluster: clinical implications of the smallest deletion.
abstract: BACKGROUND
  HOXA genes cluster plays a fundamental role in embryologic development. Deletion of the entire cluster is known to cause a clinically recognizable syndrome with mild developmental delay, characteristic facies, small feet with unusually short and big halluces, abnormal thumbs, and urogenital malformations. The clinical manifestations may vary with different ranges of deletions of HOXA cluster and flanking regions.
  
  
  METHODS
  We report a girl with the smallest deletion reported to date involving the entire HOXA cluster at 7p15.2-p14.3. The patient was the third child born to a healthy and non-consanguineous Italian couple. She was born at the 34th week of gestation by caesarean section due to cholestasis of pregnancy. Her birth weight, length, and occipitofrontal circumference were 2,140 g (25-50th centile), 46 cm (50th centile), and 33 cm (75-90th centile), respectively. The Apgar scores were 8 at both the 1st and 5th minutes. The patient presented with typical mild facial anomalies, hand and feet abnormalities, urinary anomalies, and mild speech delay. Unexpectedly, the patient demonstrated complex unusual features of multiple episodes of oxyhemoglobin desaturation, laryngeal stridor and a branchial cyst. Chromosome analysis of the patient revealed an apparently normal karyotype at the 550 band level. Based on array comparative genomic hybridization, a 2.5 Mb interstitial deletion was detected at 7p15.2p14.3 (chr7: 26,333,553-28,859,312), involving the entire HOXA cluster and a small number of other genes as SNX10, SKAP2, EVX1, HIBADH, TAX1BP1, JAZF1, and CREB5.
  
  
  CONCLUSIONS
  This report improves our understanding of the genotype-phenotype correlations of HOXA genes cluster deletions via the identification and characterization of the smallest deletion (as well as critical region) reported to date. In particular we discuss the possible implications of preterm and haploinsufficiency in the pathogenesis of the unusual findings, furthermore opening new discussion and interpretation cues.
authors.affiliation: Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 9, Milan, 20122, Italy. lidia.pezzani@unimi.it.
authors.forename: Lidia
authors.initials: L
authors.lastname: Pezzani
authors.affiliation: Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 9, Milan, 20122, Italy. donatella.milani@policlinico.mi.it.
authors.forename: Donatella
authors.initials: D
authors.lastname: Milani
authors.affiliation: Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 9, Milan, 20122, Italy. fmp.manzoni@gmail.com.
authors.forename: Francesca
authors.initials: F
authors.lastname: Manzoni
authors.affiliation: Medical Genetics Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. marco.baccarin@policlinico.mi.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Baccarin
authors.affiliation: Medical Genetics Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. rosamaria.silipigni@unimi.it.
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Silipigni
authors.affiliation: Medical Genetics Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. s.guerneri@policlinico.mi.it.
authors.forename: Silvana
authors.initials: S
authors.lastname: Guerneri
authors.affiliation: Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 9, Milan, 20122, Italy. susanna.esposito@unimi.it.
authors.forename: Susanna
authors.initials: S
authors.lastname: Esposito
mesh_terms: D000015:Abnormalities, Multiple; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000235:genetics; D004431:Ear, External / Q000002:abnormalities; D005260:Female; D005385:Fingers / Q000002:abnormalities / Q000000981:diagnostic imaging; D056726:Genetic Association Studies; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D059785:Karyotype; D007805:Language Development Disorders / Q000235:genetics; D011859:Radiography; D014034:Toes / Q000002:abnormalities
chemical_list: D018398:Homeodomain Proteins; C099959:homeobox protein HOXA13; C088144:HoxA protein