Sanger sequencing in exonic regions of STK11 gene uncovers a novel de-novo germline mutation (c.962_963delCC) associated with Peutz-Jeghers syndrome and elevated cancer risk: case report of a Chinese patient

Abstract

BackgroundPeutz-Jeghers syndrome (PJS) is caused by mutations in the tumor suppressor gene, STK11, and is characterized by gastrointestinal hamartomas, melanin spots on the lips and the extremities, and an increased risk of developing cancer.Case presentationWe reported an isolated PJS patient who died of colon cancer, whose blood sample was collected together with all the available family members’. The entire coding region of the STK11 gene was amplified by PCR and analyzed by Sanger sequencing, through which, a novel mutation, c.962_963delCC in exon 8 was identified in this patient. This mutation causes a frameshift mutation and a premature termination at codon 358. Protein structure prediction by Swiss-Model indicated a dramatic change and partial loss of the C-terminal domain. We did not observe this mutation in both parents of the proband. Therefore, it is considered a novel de-novo mutation. Furthermore, the mutation was not found in 50 unrelated healthy people.ConclusionsThe novel mutation we reported here had not been recorded in databases or literature, and the patient who possessed it suffered from PJS and colon cancer. So our results enlarge the spectrum of STK11 variants in PJS patients. This mutation is most likely responsible for development of the PJS phenotype, especially the cancer occurrence.Electronic supplementary materialThe online version of this article (10.1186/s12881-017-0471-y) contains supplementary material, which is available to authorized users.

Analysis of deletional hereditary persistence of fetal hemoglobin/δβ‐thalassemia and δ‐globin gene mutations in Southerwestern China

“…The pathogenicity of the δ‐globin variant was evaluated using the HumDiv‐trained model in Polyphen‐2 (http://genetics.bwh.harvard.edu/pph2/) and SIFT (http://sift.jcvi.org) (Ernst et al, ). The 3D structure of the native δ‐globin protein was modeled using SWISS‐MODEL and PyMol (http://www.pymol.org) (Moriarty et al, ; Zhao et al, ).…”

The altered activity of P53 signaling pathway by STK11 gene mutations and its cancer phenotype in Peutz-Jeghers syndrome

“…2a ). Most of the mutations have been previously reported [ 25 , 27 – 29 ] except for c.924G > A (Fig. 3 ).…”

“…The results were used to performance sequence alignment according to STK11 gene sequence (NP_000446.1 and NM_000455.4 in GRCh38.p7). All experiment details above had been reported previously [ 23 , 25 ].…”

New Insights Into the Complex Mutational Landscape of Sézary Syndrome

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