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Structural modeling of the wild-type and mutant proteins. The STK11 protein is mainly comprised of three major domains: the N-terminal non-catalytic domain in red, the catalytic kinase domain in green, and the C-terminal non-catalytic regulatory domain in blue. The mutation, p.Q302X, leads to partial loss of the kinase domain and complete loss of the C-terminal end of the α-helix.
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Figure 3: Structural modeling of the wild-type and mutant proteins. The STK11 protein is mainly comprised of three major domains: the N-terminal non-catalytic domain in red, the catalytic kinase domain in green, and the C-terminal non-catalytic regulatory domain in blue. The mutation, p.Q302X, leads to partial loss of the kinase domain and complete loss of the C-terminal end of the α-helix.

Mentions: Direct sequencing of the STK11 gene showed a C-to-T transversion of nucleotide 904 in exon 7 in these two unrelated families, which altered the wild-type sequence CAG (glutamine) to the mutant sequence TAG (stop) at codon 302, and resulted in a truncation of the STK11 protein (Figure 2). Our structural prediction revealed that this mutation leads to partial loss of the kinase domain and complete loss of the C-terminal end of the α-helix (Figure 3). This mutation has not yet been described in the literature.

A novel mutation in STK11 gene is associated with Peutz-Jeghers Syndrome in Chinese patients

Wang Z, Chen Y, Wu B, Zheng H, He J, Jiang B - BMC Med. Genet. (2011)

Bottom Line: A novel mutation, c.904C > T, in exon 7 was identified in both families.A C > T substitution changed codon 302 from CAG (glutamine) to TAG (stop), truncating the STK11 protein, thus leading to the partial loss of the kinase domain and complete loss of the α-helix C-terminus.Furthermore, one PJS patient from each family was diagnosed with a visceral cancer, a colon cancer and a liver cancer respectively.

Affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

ABSTRACT

Background: Peutz-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 an increased risk of developing cancer.

Methods: Blood samples were collected from two unrelated Chinese PJS families totaling 20 individuals (9 male and 11 females), including 6 PJS patients. The entire coding region of the STK11 gene was amplified by polymerase chain reaction and analyzed by direct sequencing.

Results: A novel mutation, c.904C > T, in exon 7 was identified in both families. A C > T substitution changed codon 302 from CAG (glutamine) to TAG (stop), truncating the STK11 protein, thus leading to the partial loss of the kinase domain and complete loss of the α-helix C-terminus. Furthermore, one PJS patient from each family was diagnosed with a visceral cancer, a colon cancer and a liver cancer respectively.

Conclusion: We predict that this novel mutation, p.Q302X, is most likely responsible for development of the PJS phenotype and may even contribute to malignancy.

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