RESUMEN
Peutz-Jeghers syndrome (PJS) is a rare hereditary disorder linked to increased cancer risk due to specific genetic variants in the STK11 gene. This study aimed to assess disease manifestations, genetic profiles, and genotype-phenotype correlations in PJS patients. Twenty patients from 14 families with PJS who were followed up at our clinic between 2011 and 2021 were included. Genetic susceptibility to hereditary cancers was assess-ed using targeted next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) of the STK11 gene. Clinical data were also collected and analyzed in conjunction with the genetic findings. Initial symptoms appeared around 18.9 years, predominantly abdominal pain and intussusception. Mucocutaneous lesions were found in 85%, and hamartomatous polyps in 90%. Dysplastic polyps were found in 4 patients, with 3 cases of malignancy. Nextgeneration sequencing identified 11 pathogenic and 3 likely pathogenic mutations, including 3 novel STK11 variants (LRG_319: c.598- 8_601del, LRG_319: c.708_718del, and LRG_319: c.146_147del). Next-generation sequencing diagnostic rate was 78.5% (11/14), and the overall diagnostic rate with NGS and MLPA studies was 85.7% (12/14). Patients without STK11 mutations had later symptom onset and potentially lower cancer risk. Truncated mutations are associated with earlier symptoms and elevated cancer risk. This is the first PJS case series in Turkey using the NGS and MLPA methods. It reports 3 novel mutations and emphasizes the genotype-phenotype relationship of PJS. With further studies, the genotype-phenotype relationship of STK11 variants will be better understood.
Asunto(s)
Quinasas de la Proteína-Quinasa Activada por el AMP , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Síndrome de Peutz-Jeghers , Proteínas Serina-Treonina Quinasas , Humanos , Síndrome de Peutz-Jeghers/genética , Síndrome de Peutz-Jeghers/complicaciones , Femenino , Masculino , Adulto , Adolescente , Proteínas Serina-Treonina Quinasas/genética , Adulto Joven , Mutación , Estudios de Asociación Genética , Persona de Mediana Edad , Niño , Fenotipo , Reacción en Cadena de la Polimerasa Multiplex , Dolor Abdominal/etiología , Dolor Abdominal/genéticaRESUMEN
Abstract Objective: We aimed to reveal whether there is nasal involvement by examining the Nasal Mucociliary Clearance (NMC) and the relationship between this activity and disease severity in Rheumatoid Arthritis (RA) patients. Methods: In this prospective study, NMC time, disease activity (Disease Activity Score 28) and blood parameters of RA patients (n = 87) were investigated and compared with the healthy control group (n = 50). In addition, the relationship between DAS 28 and NMC was investigated. Results: The mean NMC of the RA group was 9.51 ± 3.54 min, the mean NMC of the control group was 8.69 ± 2.85 min, and there was no significant difference between the two groups. There was no correlation between NMC and disease duration, and DAS 28. The mean NMC of the RA patients with Anti Cyclic Citrulled Peptide (Anti-CCP) positive was significantly higher than the negative ones. Conclusion: Although there was no significant difference in NMC values between the RA and control group, the NMC of the Anti-CCP positive patients was higher. Level of evidence: Level 2.