title: A single gene deletion on 4q28.3: PCDH18--a new candidate gene for intellectual disability?
abstract: We report a boy with severe developmental delay, seizures, microcephaly, hypoplastic corpus callosum, internal hydrocephalus and dysmorphic features (narrow forehead, round face, deep-set eyes, blue sclerae, large and prominent ears, nose with anteverted nares, thin upper lip, small and wide-spaced teeth, hyperextensibility of the elbows, wrists, and fingers, fingertip pads, broad hallux, sacral dimple), carrying a 1.53 Mb interstitial deletion at 4q28.3. The deletion was detected by Agilent 105K oligo-array genome hybridization and involves the genomic region between 137,417,338 and 138,947,282 base pairs on chromosome 4 (NCBI build 36). The alteration was inherited from a healthy mother and contains a single gene, PCDH18 which encodes a cadherin-related neuronal receptor thought to play a role in the establishment and function of cell-cell connections in the brain. Thus, haploinsufficiency of this gene may contribute to altered brain development and associated malformations. We found that this deletion is a private inherited copy number variation that is associated with specific clinical findings in our patient and propose the PCDH18 gene as a possible candidate gene for intellectual disability.
authors.affiliation: Department of Human and Medical Genetics, Vilnius University, LT-08661 Vilnius, Lithuania. jurate.kasnauskiene@santa.lt
authors.forename: Jurate
authors.initials: J
authors.lastname: Kasnauskiene
authors.forename: Zivile
authors.initials: Z
authors.lastname: Ciuladaite
authors.forename: Egle
authors.initials: E
authors.lastname: Preiksaitiene
authors.forename: Aušra
authors.initials: A
authors.lastname: Matulevičienė
authors.forename: Angelos
authors.initials: A
authors.lastname: Alexandrou
authors.forename: George
authors.initials: G
authors.lastname: Koumbaris
authors.forename: Carolina
authors.initials: C
authors.lastname: Sismani
authors.forename: Ingrida
authors.initials: I
authors.lastname: Pepalytė
authors.forename: Philippos C
authors.initials: PC
authors.lastname: Patsalis
authors.forename: Vaidutis
authors.initials: V
authors.lastname: Kučinskas
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics*; D002675:Child, Preschool; D002872:Chromosome Deletion; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D057895:Haploinsufficiency / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D008969:Molecular Sequence Data; D000091363:Protocadherins
chemical_list: D015820:Cadherins; C438604:PCDH18 protein, human; D000091363:Protocadherins