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A novel INDEL mutation in the PTCH1 gene in a Chinese family with Gorlin syndrome.

ABSTRACT: Gorlin syndrome is a rare autosomal dominant disorder, and 50% of the cases are due to the mutation of PTCH1, the major receptor of the hedgehog signaling pathway. Here we report a new Gorlin syndrome family found in Xinzhou, China. A further sequence analysis found a novel PTCH1 INDEL mutation, NM_001083602.2: c.1516_1524delinsTGAGCTGGAGCTCCG (p. Ala506*), leading an N Terminal truncated protein. This truncated PTCH1 was considered as non-functional version as it loses almost all functional domains, including the 4-12 transmembrane domains and the intracellular and extracellular domains accordingly. Although the effect of the N-terminal truncated PTCH1 is not clear, Gorlin syndrome in these cases is due to haploinsufficiency. Our report enriches the Gorlin syndrome database and will help to unveil the molecular basis of this condition.

SUBMITTER: Huang Z

PROVIDER: S-EPMC6963077 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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A novel INDEL mutation in the PTCH1 gene in a Chinese family with Gorlin syndrome.

Huang Zhuoya Z Zhou Yongan Y Fu Xiaoxia X Kou Aiping A Fu Hairong H Xiao Han H Jin Ying Y Zhao Zhonghua Z

International journal of clinical and experimental pathology 20181201 12

Gorlin syndrome is a rare autosomal dominant disorder, and 50% of the cases are due to the mutation of PTCH1, the major receptor of the hedgehog signaling pathway. Here we report a new Gorlin syndrome family found in Xinzhou, China. A further sequence analysis found a novel PTCH1 INDEL mutation, NM_001083602.2: c.1516_1524delinsTGAGCTGGAGCTCCG (p. Ala506*), leading an N Terminal truncated protein. This truncated PTCH1 was considered as non-functional version as it loses almost all ...[more]

PMID: 31949694

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Project description:Gorlin syndrome or nevoid basal cell carcinoma syndrome is a rare genetic disease characterized by predisposition to congenital defects, basal cell carcinomas and medulloblastoma. The syndrome results from a heritable mutation in PATCHED1 (PTCH1), causing constitutive activation of the Hedgehog pathway. The present study described a patient with Gorlin syndrome who presented early in life with characteristic basal cell carcinomas and later developed a small cell glioblastoma (GBM), World Health Organization grade IV, associated with a Patched 1 (PTCH1) N97fs*43 mutation. Comprehensive genomic profiling of GBM tissues also revealed multiple co-occurring alterations including cyclin-dependent kinase 4 (CDK4) amplification, receptor tyrosine-protein kinase 3 (ERBB3) amplification, a fibroblast growth factor receptor 1 and transforming acidic coiled-coil containing protein 1 (FGFR1-TACC1) fusion, zinc finger protein (GLI1) amplification, E3 ubiquitin-protein ligase (MDM2) amplification and spectrin α chain, erythrocytic 1 (SPTA1) T1151fs*24. After the biopsy, imaging revealed extensive leptomeningeal enhancement intracranially and around the cervical spinal cord due to leptomeningeal disease. The patient underwent craniospinal radiation followed by 6 months of adjuvant temozolomide (150 mg/m2) with good response. She was then treated with vismodegib for 11 months, first combined with temozolomide and then with bevacizumab, until disease progression was noted on MRI, with no significant toxicities associated with the combination therapy. She received additional therapies but ultimately succumbed to the disease four months later. The current study presents the first documentation in the literature of a primary (non-radiation induced) glioblastoma secondary to Gorlin syndrome. Based on this clinical experience, vismodegib should be considered in combination with standard-of-care therapies for patients with known Gorlin syndrome-associated glioblastomas and sonic hedgehog pathway mutations.

Dataset Information

A novel INDEL mutation in the PTCH1 gene in a Chinese family with Gorlin syndrome.

Publications

A novel INDEL mutation in the <i>PTCH1</i> gene in a Chinese family with Gorlin syndrome.

Similar Datasets

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