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BMC Microbiology Nov 2023Peutz-Jeghers Syndromeis a rare autosomal dominant genetic disease characterized by gastrointestinal hamartomatous polyps and skin and mucous membrane pigmentation. The...
Peutz-Jeghers Syndromeis a rare autosomal dominant genetic disease characterized by gastrointestinal hamartomatous polyps and skin and mucous membrane pigmentation. The pathogenesis of PJS remains unclear; however, it may be associated with mutations in the STK11 gene, and there is currently no effective treatment available. The gut microbiota plays an important role in maintaining intestinal homeostasis in the human body, and an increasing number of studies have reported a relationship between gut microbiota and human health and disease. However, relatively few studies have been conducted on the gut microbiota characteristics of patients with PJS. In this study, we analyzed the characteristics of the gut microbiota of 79 patients with PJS using 16 S sequencing and measured the levels of short-chain fatty acids in the intestines. The results showed dysbiosis in the gut microbiota of patients with PJS, and decreased synthesis of short-chain fatty acids. Bacteroides was positively correlated with maximum polyp length, while Agathobacter was negatively correlated with age of onset. In addition, acetic acid, propionic acid, and butyric acid were positively correlated with the age of onset but negatively correlated with the number of polyps. Furthermore, the butyric acid level was negatively correlated with the frequency of endoscopic surgeries. In contrast, we compared the gut microbiota of STK11-positive and STK11-negative patients with PJS for the first time, but 16 S sequencing analysis revealed no significant differences. Finally, we established a random forest prediction model based on the gut microbiota characteristics of patients to provide a basis for the targeted diagnosis and treatment of PJS in the future.
Topics: Humans; Peutz-Jeghers Syndrome; Gastrointestinal Microbiome; Germ-Line Mutation; Fatty Acids, Volatile; Butyrates
PubMed: 38036954
DOI: 10.1186/s12866-023-03132-0 -
Revista de Gastroenterologia de Mexico... 2020Peutz-Jeghers syndrome is a rare autosomal dominant inherited disease caused by a germline mutation of the STK11/LKB1 gene, located on chromosome 19p13.3. It is... (Observational Study)
Observational Study
INTRODUCTION AND OBJECTIVES
Peutz-Jeghers syndrome is a rare autosomal dominant inherited disease caused by a germline mutation of the STK11/LKB1 gene, located on chromosome 19p13.3. It is characterized by mucocutaneous hyperpigmentation, hamartomatous polyposis, and predisposition to cancer. The aim of the present study was to identify and register patients with Peutz-Jeghers syndrome, describe the disease, and estimate its prevalence in Valencia (Spain).
MATERIALS AND METHODS
A print-out of the clinical histories from 10 hospitals was obtained utilizing the ICD-9 code 759.6 from the Minimum Basic Data Set of Hospital Admissions of the Spanish Ministry of Health and Consumer Affairs.
RESULTS
From a total of 405 clinical histories found, 15 (9 males and 6 females) fit the diagnostic criteria of Peutz-Jeghers syndrome. Mean age at diagnosis was 13.8 years and mean age at death was 54.2 years. Four males died, all from cancer. The estimated disease prevalence was 0.4/100,000 inhabitants. All the patients presented with anemia and polyps in the small bowel (80% in the duodenum, 66.7% in the ileum, and 40% in the jejunum), 93.3% underwent urgent surgical intervention and presented with intestinal invagination, and 40% of the patients developed cancer at a mean age of 48.5 years.
CONCLUSION
The present study is the first register of patients with Peutz-Jeghers syndrome in Valencia, Spain. The ICD-9 code is nonspecific for rare diseases. The duodenum was the most frequent location for polyps and the majority of cases presented with intestinal invagination, bowel obstruction, and urgent surgical intervention. A large percentage of patients presented with cancer. It would be of interest to review and evaluate the existing surveillance protocols in the Valencian Community.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Follow-Up Studies; Genetic Markers; Genetic Testing; Humans; Infant; Male; Middle Aged; Peutz-Jeghers Syndrome; Prevalence; Registries; Retrospective Studies; Spain; Young Adult
PubMed: 31257110
DOI: 10.1016/j.rgmx.2019.02.005 -
World Journal of Gastroenterology Oct 2021Different types of pathogenic mutations may produce different clinical phenotypes, but a correlation between Peutz-Jeghers syndrome (PJS) genotype and clinical phenotype...
BACKGROUND
Different types of pathogenic mutations may produce different clinical phenotypes, but a correlation between Peutz-Jeghers syndrome (PJS) genotype and clinical phenotype has not been found. Not all patients with PJS have detectable mutations of the gene, what is the genetic basis of clinical phenotypic heterogeneity of PJS? Do PJS cases without mutations have other pathogenic genes? Those are clinical problems that perplex doctors.
AIM
The aim was to investigate the specific gene mutation of PJS, and the correlation between the genotype and clinical phenotype of PJS.
METHODS
A total of 24 patients with PJS admitted to the Air Force Medical Center, PLA (formerly the Air Force General Hospital, PLA) from November 1994 to January 2020 were randomly selected for inclusion in the study. One hundred thirty-nine common hereditary tumor-related genes including were screened and analyzed for pathogenic germline mutations by high-throughput next-generation sequencing (NGS). The mutation status of the genes and their relationship with clinical phenotypes of PJS were explored.
RESULTS
Twenty of the 24 PJS patients in this group (83.3%) had gene mutations, 90% of which were pathogenic mutations, and ten had new mutation sites. Pathogenic mutations in exon 7 of gene were significantly lower than in other exons. Truncation mutations are more common in exons 1 and 4 of , and their pathogenicity was significantly higher than that of missense mutations. We also found gene mutations in PJS patients.
CONCLUSION
PJS has a relatively complicated genetic background. Changes in the sites responsible for coding functional proteins in exon 1 and exon 4 of may be one of the main causes of PJS. Mutation of the gene may be a cause of genetic heterogeneity in PJS.
Topics: AMP-Activated Protein Kinase Kinases; Exons; Germ-Line Mutation; Humans; Mutation; Peutz-Jeghers Syndrome; Phenotype; Protein Serine-Threonine Kinases; Recombinases
PubMed: 34754157
DOI: 10.3748/wjg.v27.i39.6631 -
Ochsner Journal 2020The field of hereditary cancer syndromes and genetic testing for patients and families is a rapidly evolving discipline, with an emphasis on cancer prevention. We... (Review)
Review
The field of hereditary cancer syndromes and genetic testing for patients and families is a rapidly evolving discipline, with an emphasis on cancer prevention. We review the literature regarding the most common genetic syndromes associated with gynecologic malignancies and discuss the management of these conditions. We also examine the logistic process surrounding cancer genetic testing and identify some perceived barriers. Five genetic syndromes are known to be associated with gynecologic malignancies: hereditary breast and ovarian cancer, Lynch, Cowden, Peutz-Jeghers, and Li-Fraumeni. Each is associated with varying risks of breast, ovarian, and uterine malignancies. The National Comprehensive Cancer Network guidelines regarding the management of these syndromes are focused primarily on reducing the risk of developing gynecologic malignancies. However, great complexity is involved with genetic testing for patients and their families, and barriers exist for the widespread use and implementation of such testing. Genetic testing is fundamental to primary cancer prevention and to oncologic care. Physicians, payers, and institutions must work collaboratively to maximize genetic testing with the goals of primary cancer prevention and treatment.
PubMed: 33408585
DOI: 10.31486/toj.20.0051 -
Familial Cancer Sep 2011
Topics: AMP-Activated Protein Kinase Kinases; Humans; Neoplasms; Peutz-Jeghers Syndrome; Protein Serine-Threonine Kinases
PubMed: 21874563
DOI: 10.1007/s10689-011-9474-6 -
BioMed Research International 2020Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited disease caused by a germline mutation in the gene. It is characterized by mucocutaneous...
BACKGROUND
Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited disease caused by a germline mutation in the gene. It is characterized by mucocutaneous pigmentation, gastrointestinal hamartomatous polyps, and cancer predisposition.
AIMS
We aimed to summarize the main clinical and genetic features of Chinese PJS patients and assessed the genotype-phenotype correlations.
METHODS
Thirty-eight patients clinically diagnosed with Peutz-Jeghers syndrome were included in this study from 2016 to 2019. Combined direct sequencing and multiplex ligation-dependent probe amplification tests were used to detect germline heterogeneous mutations. RNA sequencing was performed in polyps of PJS patients and control groups to evaluate the difference in expression of . The genotype-phenotype correlations were calculated by Kaplan-Meier analyses.
RESULTS
All 26 probands and 12 affected relatives had germline heterogeneous mutations among which 8 variants were novel. Individuals with missense mutations had their first surgery and other symptoms significantly later than individuals with null mutations.
CONCLUSION
This study expanded the spectrum of gene mutations and further elucidated individuals with null mutations of typically had an earlier onset of PJS symptoms and needed earlier management.
Topics: AMP-Activated Protein Kinase Kinases; Adolescent; Adult; Asian People; Child; Child, Preschool; China; Cohort Studies; Female; Germ-Line Mutation; Humans; Male; Middle Aged; Peutz-Jeghers Syndrome; Protein Serine-Threonine Kinases; Young Adult
PubMed: 32462036
DOI: 10.1155/2020/9159315 -
Best Practice & Research. Clinical... 2022Juvenile polyposis syndrome (JPS) is a rare precancerous condition that confers an increased risk of developing gastrointestinal cancers. The inheritance pattern is... (Review)
Review
Juvenile polyposis syndrome (JPS) is a rare precancerous condition that confers an increased risk of developing gastrointestinal cancers. The inheritance pattern is autosomal dominant. JPS should be clinically suspected when the other hamartomatous polyposis syndromes are excluded (i.e., Peutz- Jeghers and Cowden), in presence of numerous juvenile polyps in the colorectum or in other GI locations. Among the syndromic features, JPS can present with concomitant extra-intestinal manifestations, above all cutaneous manifestations such as telangiectasia, pigmented nevi, and skeletal stigmata. Pathogenic germline variants of either BMPR1A or SMAD4 cause the syndrome. In JPS a cumulative risk of CRC of 39-68% has been estimated. The oncological risk justifies and imposes prevention strategies that aim at the cancer risk reduction through endoscopic screening, as recommended by international scientific societies. The aim of this review is to summarize clinical and genetic features of JPS and to elucidate the steps of the clinical management from diagnosis to surveillance.
Topics: Colorectal Neoplasms; Gastrointestinal Neoplasms; Humans; Intestinal Polyposis; Neoplastic Syndromes, Hereditary; Peutz-Jeghers Syndrome
PubMed: 35988962
DOI: 10.1016/j.bpg.2022.101799 -
Cureus Apr 2022A 20-year-old female patient with a family history significant for Peutz-Jeghers syndrome presented to the hospital multiple times with complaints of abdominal pain....
A 20-year-old female patient with a family history significant for Peutz-Jeghers syndrome presented to the hospital multiple times with complaints of abdominal pain. On the initial visit to the hospital, the patient underwent small bowel resection for small bowel obstruction secondary to intussusception, following which she visited the hospital again one year later for similar complaints and underwent reduction of multiple points of intussusception of the small bowel without any resection of the same. Eventually, the patient underwent resection of the small bowel for the second time, along with tumor resections. The importance of follow-up in patients with Peutz-Jeghers is particularly essential, in part, because it is vital to monitor the tumors, their size, and number to prevent surgical intestinal complications, anemia, and also to eventually monitor for carcinomatous changes.
PubMed: 35530863
DOI: 10.7759/cureus.23792 -
Journal of Medical Genetics Dec 1997Peutz-Jeghers syndrome (PJS, MIM 175,2000) is a disease of autosomal dominant inheritance that is characterised by hamartomatous gastrointestinal polyps and... (Review)
Review
Peutz-Jeghers syndrome (PJS, MIM 175,2000) is a disease of autosomal dominant inheritance that is characterised by hamartomatous gastrointestinal polyps and mucocutaneous pigmentation. In addition to problems such as intussusception, PJS predisposes to cancers of several sites. The unusual combination of clinical features makes the identification of the defect underlying PJS particularly interesting. Recently, the PJS gene has been mapped to chromosome 19p13.
Topics: Adult; Female; Humans; Male; Middle Aged; Peutz-Jeghers Syndrome
PubMed: 9429144
DOI: 10.1136/jmg.34.12.1007 -
Journal of Indian Association of... 2023Peutz-Jeghers Syndrome (PJS) is an autosomal dominant disease presenting with hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on lips and...
INTRODUCTION
Peutz-Jeghers Syndrome (PJS) is an autosomal dominant disease presenting with hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on lips and oral mucosa. The incidence of this syndrome is approximately 1 in 1,20,000 births.
MATERIALS AND METHODS
In this article, we are presenting 11 cases of PJS which were misdiagnosed and patients were compelled to visit hospital repeatedly. All these cases were diagnosed based on clinical suspicion, family history, and histopathological examination of specimens. Most of the cases presented with intussusception and required emergency surgical management.
RESULTS
PJS can be diagnosed by the presence of microscopically confirmed hamartomatous polyps and a minimum of two of the following clinical criteria: Family history, mucocutaneous melanotic spots, and small bowel polyps with bleeding per rectally. The diagnosis can be missed if the melanotic spots on the face are missed. Routine investigations, imaging, and endoscopy were done in all cases. PJS patients need regular follow-up due to chance of recurrence of symptoms and susceptibility to cancer.
CONCLUSION
PJS needs a high index of suspicion for diagnosis in cases of recurrent abdominal pain with bleeding per rectum. Proper family history and meticulous clinical examination for melanosis are very important to prevent the misdiagnosis of these cases.
PubMed: 37389385
DOI: 10.4103/jiaps.jiaps_197_21