OBJECTIVE: To screen for pathogenic variants in the coding regions of STK11 gene among Chinese patients with Peutz-Jeghers syndrome (PJS). METHODS: Peripheral blood samples were collected from 64 patients. The coding regions of the STK11 gene were detected by PCR and Sanger sequencing. RESULTS: Fourty-eight patients were found to harbor STK11 gene variants, which included 39 types of variants consisting of missense, nonsense, insertional, deletional and splice site variants. Among 64 PJS patients, the detection rate of point variants was 75.00% (48/64), of which missense variants accounted for 29.17% (14/48), nonsense variants accounted for 29.17%(14/48), insertion variants accounted for 2.08% (1/48), deletional variants accounted for 10.42% (5/48), and splice site variants accounted for 29.17% (14/48). The detection rates of sporadic cases and those with a family history were 71.8% (28/39) and 80.0% (20/25), respectively. Two variants (c.250A>T, c.580G>A) occurred in 3 PJS probands. Thirteen variants were unreported previously and were considered to be pathogenic. CONCLUSION The detection rate of variants among Chinese PJS patients is similar to that of other countries. A number of novel common variant sites were discovered, which enriched the spectrum of PJS-related variants.
Asian Continental Ancestry Group ; China ; DNA Mutational Analysis ; Humans ; Peutz-Jeghers Syndrome ; genetics ; Protein-Serine-Threonine Kinases ; genetics

To explore the clinical features, pathological features, gene test results, diagnosis, treatment and prognosis of Peutz-Jeghers syndrome(PJS).
 Methods: We retrospectively analyzed clinical data of 46 hospitalized cases of PJS during 2007 and 2017.
 Results: All 46 patients had mucocutaneous melanin pigmentation and multiple gastrointestinal polyposis. The pigmentation was first noticed often within 5 years old, and 14 cases had family history. The clinical manifestations mainly included black spots, abdominal pain, hematochezia, and anemia. Histological examinations showed that 20 patients were classified as hamartomatous polyps,18 as adenomatous polyps, 14 as inflammatory polyps, and 10 as zigzag polyps. Eleven patients sequenced a panel of 20 genes previously associated with colorectal cancer (CRC) by next-generation sequencing, and the results showed 5 patients with gene mutations, and 3 of them with intussusception and surgical histories were found to have pathogenic germline mutations in the STK11 gene. Endoscopic treatment was the main therapy, but endoscopy combined with laparoscopy or surgical treatment was performed when complications occurred or the polyp was too large. Malignant tumors were found in 3 patients during follow-up.
 Conclusion: PJS is a hereditary disease which is characterized by spots of the skin or mucosa and gastrointestinal multiple polyps. The main pathological features are hamartoma and adenoma. The risks for intussusception and surgical operation are found to be high in the patients with pathogenic germline mutations in the STK11 gene. Endoscopic treatment is the main therapy. PJS patients should be followed up regularly due to the increasing risk for cancer and being easily to relapse.
Child, Preschool ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; Neoplasm Recurrence, Local ; diagnosis ; pathology ; surgery ; therapy ; Peutz-Jeghers Syndrome ; diagnosis ; surgery ; therapy ; Protein-Serine-Threonine Kinases ; genetics ; Retrospective Studies

OBJECTIVETo correlate the clinical characteristics with mutations of the STK11 and FHIT genes in 16 patients with Peutz-Jeghers syndrome (PJS).

METHODSPotential mutations in the coding regions and flanking sequences of the STK11 and FHIT genes were detected with PCR and Sanger sequencing.

RESULTSOf the 16 patients with PJS, 8 had novel mutations in the coding region of the STK11 gene, 1 had a previously reported mutation. 1 carried a mutation in the exon 10 of the FHIT gene, which is a non-coding region. None of the mutations was detected in the immediate family members. None of the patients with STK11 gene mutations had mutation in the FHIT gene. The mutation rate of the STK11 gene among patients with PJS was 56.25%.

CONCLUSIONMutations of the STK11 gene are the major cause of PJS. Few such patients had mutations of the FHIT gene. Mutations of the FHIT gene may play a part in the pathogenesis of PJS.

Acid Anhydride Hydrolases ; genetics ; Adolescent ; Adult ; Base Sequence ; Child ; DNA Mutational Analysis ; Exons ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation ; Neoplasm Proteins ; genetics ; Pedigree ; Peutz-Jeghers Syndrome ; genetics ; Protein-Serine-Threonine Kinases ; genetics ; Young Adult

Peutz-Jeghers syndrome (PJS) is a very rare genetic disorder. PJS carries a high risk of developing gastrointestinal (GI) cancer or non-GI cancer with advancing years. However, major symptoms of PJS in childhood are obstruction, intussusception, and bleeding from hamartomatous intestinal polyps which in majority of cases are not related to cancer. Generally, first GI symptom develops by 20 years in one half of children diagnosed with PJS. Children under two years of age who had PJS polyp-related intestinal symptoms are rare, and there have been no published report on intestinal carcinoma development, adenomatous change or dysplasia of polyps in Korean children with PJS. Recently, the authors have experienced a case PJS with adenomatous polyp change in a 15-month-old boy who had STK11 gene mutation. Therefore, early evaluation could be necessary and considered in children with PJS.
Adenoma/*diagnosis/pathology ; Base Sequence ; Colonoscopy ; Heterozygote ; Humans ; Infant ; Male ; Peutz-Jeghers Syndrome/*diagnosis/genetics/pathology ; Polymorphism, Single Nucleotide ; Polyps/pathology ; Protein-Serine-Threonine Kinases/chemistry/genetics

OBJECTIVETo investigate STK11 gene mutation in a pedigree with Peutz-Jeghers syndrome (PJS).

METHODSA pedigree of PJS was investigated. DNA was extracted from peripheral blood samples from affected and unaffected members of the pedigree and 100 unrelated healthy controls. PCR was performed to amplify all of the 9 coding exons of STK11 gene. PCR products were directly sequenced to detect mutation.

RESULTSA missense mutation p.F354L (c.1062C>G) in exon 8 of the STK11 gene has been identified in all patients with PJS, but was not found in normal individuals from the pedigree and 100 unrelated controls.

CONCLUSIONA missense mutation p.F354L of STK11 gene probably underlies the disease in this pedigree.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; DNA Mutational Analysis ; Exons ; Female ; Humans ; Male ; Molecular Sequence Data ; Pedigree ; Peutz-Jeghers Syndrome ; diagnosis ; enzymology ; genetics ; Protein-Serine-Threonine Kinases ; genetics

OBJECTIVETo investigate clinical characteristics and mutation of the LKB1 gene in a Peutz-Jeghers syndrome (PJS) pedigree.

METHODClinical data of a PJS family were analyzed and LKB1 gene mutation was detected by systematic screening with multiplex ligation-dependent probe amplification (MLPA) and DNA sequencing. Meanwhile, two hundred and fifty healthy adults were enrolled in this study and denaturing high performance liquid chromatography (PCR-DHPLC) was carried out to verify the mutation excluding polymorphism sites found in this family. Changes in protein structure and function caused by the mutated coding sequence was analyzed by SWISS-MODEL software.

RESULTThe proband had pigmented mucocutaneous lesions and multiple hamartomatous polyps in the gastrointestinal tract. There was no fragment deletion of LKB1 gene detected by MLPA. Among PJS family and 250 healthy adults, germline mutation c. 924G > C of LKB1 which cause Trp308Cys in protein sequence was identified only in the proband and another affected member. LKB1 protein activity could be reduced due to changes in LKB1 protein conformation structure by Trp308Cys.

CONCLUSIONPeutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterised by mucocutaneous pigmentation, multiple gastrointestinal hamartomatous polyps and heredofamilial nature. Gene identification and mutagen screening of LKB1 gene in all PJS patients and first degree relatives will contribute to a definite diagnosis and improve the life span of the family.

Base Sequence ; Child ; DNA Mutational Analysis ; Genetic Predisposition to Disease ; Humans ; Male ; Multiplex Polymerase Chain Reaction ; Mutation ; Mutation, Missense ; Pedigree ; Peutz-Jeghers Syndrome ; genetics ; pathology ; Polymerase Chain Reaction ; Protein-Serine-Threonine Kinases ; genetics ; Sequence Analysis, DNA

Peutz-Jeghers syndrome is an autosomal dominant inherited disorder characterized by multiple gastrointestinal hamartomatous polyps and mucocutaneous pigmentation. Peutz-Jeghers syndrome has an incidence of approximately 1 in 25,000 to 300,000 births. Crohn's disease is a chronic inflammatory bowel disease that typically manifests as regional enteritis with its incidence ranging from 3.1 to 14.6 cases per 100,000 person-years in North America. Herein, we report a case of a 30-year-old male patient who had both Peutz-Jeghers syndrome and Crohn's disease. We believe that this is the first case in Korea and the second report in the English literatures on Peutz-Jeghers syndrome coincidentally accompanied by Crohn's disease.
Adult ; Crohn Disease/complications/*diagnosis/pathology ; Endoscopy, Gastrointestinal ; Humans ; Intestinal Obstruction/etiology ; Intestinal Perforation/etiology ; Intestinal Polyps/pathology/surgery ; Male ; Peutz-Jeghers Syndrome/complications/*diagnosis/genetics ; Protein-Serine-Threonine Kinases/genetics

Adenomatous Polyposis Coli ; diagnosis ; drug therapy ; genetics ; surgery ; Antineoplastic Agents ; therapeutic use ; Colectomy ; Colorectal Neoplasms, Hereditary Nonpolyposis ; diagnosis ; drug therapy ; genetics ; surgery ; DNA Mismatch Repair ; Humans ; Ileostomy ; Peutz-Jeghers Syndrome ; diagnosis ; drug therapy ; genetics ; surgery

OBJECTIVETo screen for potential mutations of LKB1 gene in Chinese familial Peutz-Jeghers syndrome (PJS) patients and analyze their clinical manifestations.

METHODSEleven PJS families were collected and genomic DNA of peripheral blood was extracted. Typically mucosal pigmentation and hamartomatous polyps were present in all 11 probands. Mutation screening of the probands were carried out by PCR and direct sequencing. Two hundred and fifty healthy adults were enrolled as normal controls, for whom genomic DNA of peripheral blood was also extracted. PCR-denaturing high performance liquid chromatography was carried out to verify the mutation identified in the patients.

RESULTSNine germline mutations were identified in eight PJS patients, which included 7 point mutations, 1 deletion and 1 insertion. Among these, 4 were considered to be pathogenic, of which 2 were de novel, 4 were considered to be polymorphism, and 1 was uncertain.

CONCLUSIONLKB1 gene mutations with pathogenic effect are a common cause of familial PJS in Chinese patients. Most mutations are point mutations.

Adolescent ; Adult ; Base Sequence ; China ; Female ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Peutz-Jeghers Syndrome ; genetics ; Protein-Serine-Threonine Kinases ; genetics ; Young Adult

OBJECTIVETo analyze the sequence of STK11 gene coding region in 20 patients with Peutz-Jeghers syndrome and identify the point mutations in STK11 gene associated with the occurrence of the disease.

METHODSBlood samples were collected from 20 inpatients with Peutz-Jeghers syndrome treated in our center between January 2009 and October 2010. The sequence of STK11 gene coding region was analyzed using PCR and DNA sequencing and compared with the normal sequence of STK11 gene.

RESULTSOf the 20 patients with Peutz-Jeghers syndrome, 14 showed STK11 gene mutations in the coding region, including 1 patient having two mutations and 13 patients with a single mutation site. In one case, sequence analysis of the STK11 gene identified a novel type of STK11 germline mutation, in which the cytosine (C)460 was substituted by guanine (G) in exon 3 to result in a new amino acid at codon 154. Four patients from 2 families were found to have a common mutation. The remaining 6 patients were not found to have mutations in STK11 gene coding region.

CONCLUSIONMutations of STK11 gene is a major cause of Peutz-Jeghers syndrome. The missense mutation of 460 C→G in exon 3 of STK11 gene is a novel mutation associated with Peutz-Jeghers syndrome.

Adult ; Asian Continental Ancestry Group ; genetics ; Codon ; DNA Mutational Analysis ; Exons ; Female ; Humans ; Male ; Mutation ; Pedigree ; Peutz-Jeghers Syndrome ; genetics ; Protein-Serine-Threonine Kinases ; genetics