title: A de novo balanced translocation t(7;12)(p21.2;p12.3) in a patient with Saethre-Chotzen-like phenotype downregulates TWIST and an osteoclastic protein-tyrosine phosphatase, PTP-oc.
abstract: Saethre-Chotzen syndrome (SCS) is an autosomal dominant craniosynostosis syndrome with variable expression. Here we report on a female infant with a de novo balanced translocation 46, XX, t(7;12)(p21.2;p12.3) and presenting at birth brachycephaly, antimongolic palpebral fissures, ocular hypertelorism, broad nose with low nasal bridge and low-set ears. This phenotype is suggestive of a subtle form of SCS, given the absence of limbs anomalies. Cloning of both breakpoints revealed that the translocation does not interrupt the TWIST1 coding region, on 7p21, known to be causative for SCS, but downregulates TWIST1 expression due to a position effect. On chromosome 12, the breakpoint translocates a shorter transcript of PTPRO gene, the osteoclastic protein-tyrosine phosphatase, PTP-oc, near to regulatory region of 7p leading to down-regulation of PTP-oc in the proband's fibroblasts. This is a confirmatory case report providing further evidence for TWIST1 haploinsufficiency in SCS, although a possible role of PTP-oc as genetic factor underlying or at least influencing the development of craniosynostosis could not be a priori excluded.
authors.affiliation: U.O. Neurochirurgia, Istituto G. Gaslini, Genova, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: De Marco
authors.forename: Alessandro
authors.initials: A
authors.lastname: Raso
authors.forename: Silvana
authors.initials: S
authors.lastname: Beri
authors.forename: Stefania
authors.initials: S
authors.lastname: Gimelli
authors.forename: Elisa
authors.initials: E
authors.lastname: Merello
authors.forename: Samantha
authors.initials: S
authors.lastname: Mascelli
authors.forename: Maurizia
authors.initials: M
authors.lastname: Baldi
authors.forename: Ave Maria
authors.initials: AM
authors.lastname: Baffico
authors.forename: Marco
authors.initials: M
authors.lastname: Pavanello
authors.forename: Armando
authors.initials: A
authors.lastname: Cama
authors.forename: Valeria
authors.initials: V
authors.lastname: Capra
authors.forename: Roberto
authors.initials: R
authors.lastname: Giorda
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gimelli
mesh_terms: D000168:Acrocephalosyndactylia / Q000175:diagnosis / Q000235:genetics*; D001921:Brain / Q000473:pathology; D002675:Child, Preschool; D056905:Chromosome Breakpoints; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D007621:Karyotyping; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000235:genetics*; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics*; D051879:Twist-Related Protein 1 / Q000235:genetics*
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D051879:Twist-Related Protein 1; C516888:PTPRO protein, human; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3