Background: Gorlin syndrome, also known as basal cell nevus syndrome (BCNS), is a rare autosomal dominant genetic condition, characterized by the presence of multiple basal cell carcinomas at a young age, odontogenic keratocysts, skeletal anomalies, macrocephaly, and dysmorphisms. BCNS is mainly caused by mutations in PTCH1, an onco-suppressor gene that maps at 9q22.3 region. A disease related to BCNS is the 9q22.3 microdeletion syndrome. This condition has an overlapping clinical phenotype with the BCNS, but it can present in addition: metopic craniosynostosis, overgrowth, obstructive hydrocephalus, developmental delay, intellectual disability, and seizures. This syndrome is caused by the deletion of a genomic region containing the PTCH1 and the FANCC. Methods and Results: We report the case of an 11-year-old girl that came to our attention for overgrowth, dysmorphic features of the face, and craniosynostosis, but with a normal intellectual and motor development. At first we performed an array-comparative genomic hybridization (aCGH) analysis. The analysis showed no copy number changes. Then, we performed the analysis of the PTCH1 by next-generation sequencing. This analysis showed a heterozygous frameshift mutation. Conclusion: This is the first case with a PTCH1 point mutation with a 9q22.3 microdeletion syndrome phenotype. This finding may strengthen the importance of the role of the PTCH1, especially regarding the metopic craniosynostosis.

Unexpected phenotype in a frameshift mutation of PTCH1 / BELTRAMI BENEDETTA, PRADA ELISABETTA, G. Tolva, G. Scuvera, SILIPIGNI ROSAMARIA, D. Graziani, G. Bulfamante, C. Gervasini, P. Marchisio, MILANI DONATELLA. - In: MOLECULAR GENETICS & GENOMIC MEDICINE. - ISSN 2324-9269. - 8:1(2020 Jan), pp. e987.1-e987.4. [10.1002/mgg3.987]

Unexpected phenotype in a frameshift mutation of PTCH1

B. Beltrami;E. Prada
;
G. Tolva;R. Silipigni;G. Bulfamante;C. Gervasini;P. Marchisio;D. Milani
2020-01

Abstract

Background: Gorlin syndrome, also known as basal cell nevus syndrome (BCNS), is a rare autosomal dominant genetic condition, characterized by the presence of multiple basal cell carcinomas at a young age, odontogenic keratocysts, skeletal anomalies, macrocephaly, and dysmorphisms. BCNS is mainly caused by mutations in PTCH1, an onco-suppressor gene that maps at 9q22.3 region. A disease related to BCNS is the 9q22.3 microdeletion syndrome. This condition has an overlapping clinical phenotype with the BCNS, but it can present in addition: metopic craniosynostosis, overgrowth, obstructive hydrocephalus, developmental delay, intellectual disability, and seizures. This syndrome is caused by the deletion of a genomic region containing the PTCH1 and the FANCC. Methods and Results: We report the case of an 11-year-old girl that came to our attention for overgrowth, dysmorphic features of the face, and craniosynostosis, but with a normal intellectual and motor development. At first we performed an array-comparative genomic hybridization (aCGH) analysis. The analysis showed no copy number changes. Then, we performed the analysis of the PTCH1 by next-generation sequencing. This analysis showed a heterozygous frameshift mutation. Conclusion: This is the first case with a PTCH1 point mutation with a 9q22.3 microdeletion syndrome phenotype. This finding may strengthen the importance of the role of the PTCH1, especially regarding the metopic craniosynostosis.
9q22.3 microdeletion syndrome; craniosynostosis; Gorlin syndrome; PTCH1
Settore MED/38 - Pediatria Generale e Specialistica
Settore MED/08 - Anatomia Patologica
2-ott-2019
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/700050
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