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.
| Original language | English |
|---|---|
| Journal | European Journal of Medical Genetics |
| Volume | 54 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Sep 2011 |
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Keywords
- Craniosynostosis
- PTP-oc
- Saethre-Chotzen syndrome
- T(7;12)(p21.2;p12.3) translocation
- TWIST1
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
Cite this
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. / De Marco, Patrizia; Raso, Alessandro; Beri, Silvana; Gimelli, Stefania; Merello, Elisa; Mascelli, Samantha; Baldi, Maurizia; Baffico, Ave Maria; Pavanello, Marco; Cama, Armando; Capra, Valeria; Giorda, Roberto; Gimelli, Giorgio.
In: European Journal of Medical Genetics, Vol. 54, No. 5, 09.2011.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - De Marco, Patrizia
AU - Raso, Alessandro
AU - Beri, Silvana
AU - Gimelli, Stefania
AU - Merello, Elisa
AU - Mascelli, Samantha
AU - Baldi, Maurizia
AU - Baffico, Ave Maria
AU - Pavanello, Marco
AU - Cama, Armando
AU - Capra, Valeria
AU - Giorda, Roberto
AU - Gimelli, Giorgio
PY - 2011/9
Y1 - 2011/9
N2 - 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.
AB - 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.
KW - Craniosynostosis
KW - PTP-oc
KW - Saethre-Chotzen syndrome
KW - T(7;12)(p21.2;p12.3) translocation
KW - TWIST1
UR - http://www.scopus.com/inward/record.url?scp=79961126243&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79961126243&partnerID=8YFLogxK
U2 - 10.1016/j.ejmg.2011.05.007
DO - 10.1016/j.ejmg.2011.05.007
M3 - Article
C2 - 21708297
AN - SCOPUS:79961126243
VL - 54
JO - European Journal of Medical Genetics
JF - European Journal of Medical Genetics
SN - 1769-7212
IS - 5
ER -