title: A novel microdeletion syndrome at 3q13.31 characterised by developmental delay, postnatal overgrowth, hypoplastic male genitals, and characteristic facial features.
abstract: BACKGROUND
  Congenital deletions affecting 3q11q23 have rarely been reported and only five cases have been molecularly characterised. Genotype-phenotype correlation has been hampered by the variable sizes and breakpoints of the deletions. In this study, 14 novel patients with deletions in 3q11q23 were investigated and compared with 13 previously reported patients.
  
  
  METHODS
  Clinical data were collected from 14 novel patients that had been investigated by high resolution microarray techniques. Molecular investigation and updated clinical information of one cytogenetically previously reported patient were also included.
  
  
  RESULTS
  The molecular investigation identified deletions in the region 3q12.3q21.3 with different boundaries and variable sizes. The smallest studied deletion was 580 kb, located in 3q13.31. Genotype-phenotype comparison in 24 patients sharing this shortest region of overlapping deletion revealed several common major characteristics including significant developmental delay, muscular hypotonia, a high arched palate, and recognisable facial features including a short philtrum and protruding lips. Abnormal genitalia were found in the majority of males, several having micropenis. Finally, a postnatal growth pattern above the mean was apparent. The 580 kb deleted region includes five RefSeq genes and two of them are strong candidate genes for the developmental delay: DRD3 and ZBTB20.
  
  
  CONCLUSIONS
  A newly recognised 3q13.31 microdeletion syndrome is delineated which is of diagnostic and prognostic value. Furthermore, two genes are suggested to be responsible for the main phenotype.
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden. anna-maja.nystrom@slu.se
authors.forename: Anna-Maja
authors.initials: AM
authors.lastname: Molin
authors.forename: J
authors.initials: J
authors.lastname: Andrieux
authors.forename: D A
authors.initials: DA
authors.lastname: Koolen
authors.forename: V
authors.initials: V
authors.lastname: Malan
authors.forename: M
authors.initials: M
authors.lastname: Carella
authors.forename: L
authors.initials: L
authors.lastname: Colleaux
authors.forename: V
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: A
authors.initials: A
authors.lastname: David
authors.forename: N
authors.initials: N
authors.lastname: de Leeuw
authors.forename: B
authors.initials: B
authors.lastname: Delobel
authors.forename: B
authors.initials: B
authors.lastname: Duban-Bedu
authors.forename: R
authors.initials: R
authors.lastname: Fischetto
authors.forename: F
authors.initials: F
authors.lastname: Flinter
authors.forename: S
authors.initials: S
authors.lastname: Kjaergaard
authors.forename: F
authors.initials: F
authors.lastname: Kok
authors.forename: A C
authors.initials: AC
authors.lastname: Krepischi
authors.forename: C
authors.initials: C
authors.lastname: Le Caignec
authors.forename: C Mackie
authors.initials: CM
authors.lastname: Ogilvie
authors.forename: S
authors.initials: S
authors.lastname: Maia
authors.forename: M
authors.initials: M
authors.lastname: Mathieu-Dramard
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: O
authors.initials: O
authors.lastname: Palumbo
authors.forename: F
authors.initials: F
authors.lastname: Papadia
authors.forename: R
authors.initials: R
authors.lastname: Pfundt
authors.forename: W
authors.initials: W
authors.lastname: Reardon
authors.forename: A
authors.initials: A
authors.lastname: Receveur
authors.forename: M
authors.initials: M
authors.lastname: Rio
authors.forename: L
authors.initials: L
authors.lastname: Ronsbro Darling
authors.forename: C
authors.initials: C
authors.lastname: Rosenberg
authors.forename: J
authors.initials: J
authors.lastname: Sá
authors.forename: L
authors.initials: L
authors.lastname: Vallee
authors.forename: C
authors.initials: C
authors.lastname: Vincent-Delorme
authors.forename: L
authors.initials: L
authors.lastname: Zelante
authors.forename: M-L
authors.initials: ML
authors.lastname: Bondeson
authors.forename: G
authors.initials: G
authors.lastname: Annerén
mesh_terms: D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics*; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D005837:Genitalia, Male / Q000002:abnormalities*; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D050637:Receptors, Dopamine D3 / Q000235:genetics; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics
chemical_list: C493593:DRD3 protein, human; D009419:Nerve Tissue Proteins; D050637:Receptors, Dopamine D3; D014157:Transcription Factors; C427486:ZBTB20 protein, human