title: Interstitial deletion of 3p22.3p22.2 encompassing ARPP21 and CLASP2 is a potential pathogenic factor for a syndromic form of intellectual disability: a co-morbidity model with additional copy number variations in a large family.
abstract: We describe a family in which four individuals (the mother and three children) presented with an overlapping phenotype of minor physical anomalies and intellectual disability. Four previously unreported copy number variants were found inherited either from the affected mother or from the healthy father, consisting of a 3p22.3p22.2 deletion (2.5 Mb), a 3p24.3 deletion (0.55 Mb), a 6q22.31 duplication (0.74 Mb), all maternally inherited, and an 18q11.2 duplication (0.276 Mb) which was paternally inherited. The deletions on chromosome 3 were both found to segregate with the disease. However, being the 0.55 Mb deleted segment on 3p24.3 devoid of genes, we considered that the 2.5 Mb deletion on 3p22.3p22.2 acts as major pathogenic rearrangement in this condition. Among the transcribed genes residing in this interval, ARPP21 and CLASP2 are proposed as good candidate genes on the basis of their functional properties. A co-morbidity role for the other small rearrangements detected in the affected individuals in association with the 3p22.3p22.2 deletion is also suggested, according to a second-side model of pathogenesis.
authors.affiliation: Instituto di Genetica Medica, Università Cattolica del Sacro Cuore, Roma, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Marangi
authors.forename: Daniela
authors.initials: D
authors.lastname: Orteschi
authors.forename: Valentina
authors.initials: V
authors.lastname: Milano
authors.forename: Giorgia
authors.initials: G
authors.lastname: Mancano
authors.forename: Marcella
authors.initials: M
authors.lastname: Zollino
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D019066:Facies; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics*; D013577:Syndrome; D055815:Young Adult
chemical_list: C497851:CLASP2 protein, human; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; C061368:cyclic AMP-regulated phosphoprotein ARPP-21
keywords: array CGH; deletion 3p22.3p22.2; deletion 3p24.3; duplication 18q11.2; duplication 6q22.31; intellectual disability; multiple copy number variants