Clinical and Genetic Study of children With Peutz-Jeghers Syndrome Identifies a High Frequency of STK11 De Novo Mutation

Objectives: The present study aims to identify the genotype-phenotype correlation in children with Peutz-Jeghers Syndrome (PJS) through the analysis of STK11 gene mutations in the context of clinical and pathological characteristics. Method: In this observational cohort study, the clinical characteristics of 18 families diagnosed with pediatric PJS were collected. Genomic DNA from the peripheral blood of affected children and their family members was collected. The coding region of STK11 was amplified by PCR and screened for mutation by Sanger sequencing. The families that were negative for STK11 mutation were further assessed by multiplex ligation-dependent probe amplification (MLPA). Result: Initial presentation in affected children was at 1.6 to 14.2 years and included anemia in 8 patients whereas 6 presented for screening by virtue of family history. All patients underwent endoscopy, colonoscopy, and polypectomy. Polyps were distributed throughout the gastrointestinal (GI) tract, including the small intestine, stomach, colon, and rectum. In the 18 pediatric PJS families, STK11 mutations were detected in 8 families by Sanger sequencing, and large deletions were detected in 3 by MLPA, respectively. Nine of the 11 STK11 mutations were de novo, 3 were novel (c.419T>C:p.L140P, c.314T>G:p.L105X), and (c.488_489insACGG p.L164fs). Conclusions: Although the main clinical features of pediatric PJS were similar to those of PJS cases in adults, a high frequency of STK11 de novo mutations were encountered in our population of patients with PJS. Address correspondence and reprint requests to Hong-Mei Zhao, MD, Jie-Yu You, MD, Department of Gastroenterology, Hunan Children's Hospital, 86 Ziyuan Road, Changsha 410007, China (e-mails: 364875977@foxmail.com, yjy660111@sina.com). Received 27 May, 2018 Accepted 14 September, 2018 Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). This work was supported by Health and Family Planning Commission Fund of Hunan Province (B2016040 to H.M.Z.), the national natural Science Foundation of china (31501017 to Y.J.Y.) and the Key laboratory fund of Hunan Province (2018tP1028 to Z.H.X.). The authors report no conflicts of interest. © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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