Unexpected phenotype in a frameshift mutation of PTCH1

Molecular Genetics & Genomic Medicine

Cristina Gervasini¹  Daniela Graziani²  Gaetano Bulfamante²  Rosamaria Silipigni³  Elisabetta Prada⁴  Benedetta Beltrami⁴  Gianluca Tolva⁴  Donatella Milani⁴  Giulietta Scuvera⁴  Paola Marchisio⁴ 

[1] Department of Health Sciences Medical Genetics Università degli Studi di Milano Milano Italy;Department of Human Pathology Cytogenetic and Molecular Pathology ASST Santi Paolo e Carlo Milan Italy;Laboratory of Medical Genetics Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano Italy;Pediatric Highly Intensive Care Unit Department of Pathophysiology and Transplantation Università degli Studi di Milano Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano Italy;

关键词: 9q22.3 microdeletion syndrome;    craniosynostosis;    Gorlin syndrome;    PTCH1;   

DOI  :  10.1002/mgg3.987

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown