title: Cryptic 13q34 and 4q35.2 Deletions in an Italian Family.
abstract: Variations of DNA sequences in the human genome range from large, microscopically visible chromosome anomalies to single nucleotide changes. Submicroscopic genomic copy number variations, i.e. chromosomal imbalances which are undetectable by conventional cytogenetic analysis, play an intriguing clinical role. In this study, we describe the clinical consequences of the concurrent presence of an interstitial deletion in 13q34 and a terminal deletion in 4q35.2 in an Italian family. The index patient, a 19-year-old male, as well as his 12-year-old sister are carriers of both deletions, one of maternal and the other of paternal origin. The phenotype includes language delay, multiorgan involvement and bleeding diathesis with mild deficiency of factors X and VII. In the sister, the concomitant presence of Noonan syndrome may partly explain the clinical symptoms. The deleted region on chromosome 13 involves several genes (ATP11A, MCF2L, F7, F10, PROZ, PCID2, CUL4A, and LAMP1); some of these seem to play a role in the proband's phenotype. The terminal deletion in 4q35.2 contains other OMIM genes (FRG1, FRG2 and DBET); moreover, the 4q region is reported as a susceptibility locus for Crohn's disease, diagnosed in the proband's father. To our knowledge, this is the first report of a family with these 2 submicroscopic copy number changes. We tried to relate the clinical phenotype of the proband and his family to the molecular function of the involved genes.
authors.affiliation: Regional Reference Centre for Inherited Bleeding Disorders, University Hospital of Parma, Parma, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Riccardi
authors.forename: Gianna F
authors.initials: GF
authors.lastname: Rivolta
authors.forename: Vera
authors.initials: V
authors.lastname: Uliana
authors.forename: Francesca R
authors.initials: FR
authors.lastname: Grati
authors.forename: Roberta
authors.initials: R
authors.lastname: La Starza
authors.forename: Livia
authors.initials: L
authors.lastname: Marcato
authors.forename: Caterina
authors.initials: C
authors.lastname: Di Perna
authors.forename: Gabriele
authors.initials: G
authors.lastname: Quintavalle
authors.forename: Livia
authors.initials: L
authors.lastname: Garavelli
authors.forename: Simonetta
authors.initials: S
authors.lastname: Rosato
authors.forename: Gabriella
authors.initials: G
authors.lastname: Sammarelli
authors.forename: Tauro M
authors.initials: TM
authors.lastname: Neri
authors.forename: Annarita
authors.initials: A
authors.lastname: Tagliaferri
authors.forename: Davide
authors.initials: D
authors.lastname: Martorana
mesh_terms: D002648:Child; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13; D002894:Chromosomes, Human, Pair 4; D056915:DNA Copy Number Variations; D005168:Factor VII Deficiency / Q000235:genetics* / Q000473:pathology; D005171:Factor X Deficiency / Q000235:genetics* / Q000473:pathology; D005260:Female; D006474:Hemorrhagic Disorders / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D040582:Inheritance Patterns; D007558:Italy; D008297:Male; D009634:Noonan Syndrome / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D055815:Young Adult