E-Healthcare for Celiac Disease-A Multicenter Randomized Controlled Trial

To evaluate the (cost-)effectiveness of online consultations in follow-up of patients with celiac disease (CD). Multicenter randomized, controlled trial involving 304 patients aged ≤25 years with CD for ≥1 year, randomized to an online (n = 156) or outpatient consultation (n = 148). An online consultation included questionnaires for symptom and growth measurement. Antitransglutaminase-type-2 antibodies were determined using a point-of-care (POC) test. Controls had a traditional consultation with antitransglutaminase-type-2 antibodies testing in laboratories. Both groups completed questionnaires concerning CD-specific health-related quality of life (HRQOL), gluten-free diet adherence, and patient satisfaction. Six months later, participants repeated HRQOL and patient satisfaction questionnaires and the POC test. The primary outcome was anti-transglutaminase-type-2 antibodies after 6 months, and the secondary outcomes were health problems, dietary adherence, HRQOL, patient satisfaction, and costs. The performance of the POC test was inferior to laboratory testing (2/156 positive POC tests vs 13/148 positive laboratory tests; P = .003). Health problems were detected significantly more frequently using online consultation. The detection of growth problems and dietary transgressions was similar. HRQOL (from 1 [good] to 5 [poor]) improved after online consultation (from 3.25 to 3.16 [P = .013] vs controls from 3.10 to 3.23; P = .810). Patient satisfaction (from 1 [low] to 10 [high]) was 7.6 (online) vs 8.0 (controls; P = .001); 58% wished to continue online consultations. Mean costs per participant during the studied period were €202 less for the online group (P  < .001). The primary outcome could not be tested because the POC test was unreliable. Nevertheless, our results indicate that online consultations for children and young adults with CD are cost saving, increase CD-specific HRQOL, and are satisfactory for the majority. Trialregister.nl: NTR368

High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer

Purpose: In many children with cancer and characteristics suggestive of a genetic predisposition syndrome, the genetic cause is still unknown. We studied the yield of pathogenic mutations by applying whole-exome sequencing on a selected cohort of children with cancer. Experimental Design: To identify mutations in known and novel cancer-predisposing genes, we performed trio-based whole-exome sequencing on germline DNA of 40 selected children and their parents. These children were diagnosed with cancer and had at least one of the following features: (1) intellectual disability and/or congenital anomalies, (2) multiple malignancies, (3) family history of cancer, or (4) an adult type of cancer. We first analyzed the sequence data for germline mutations in 146 known cancer-predisposing genes. If no causative mutation was found, the analysis was extended to Results: Four patients carried causative mutations in a known cancer-predisposing gene: TP53 and DICER1 (n ¼ 3). In another 4 patients, exome sequencing revealed mutations causing syndromes that might have contributed to the malignancy (EP300-based Rubinstein–Taybi syndrome, ARID1A-based Coffin–Siris syndrome, ACTB-based Baraitser–Winter syndrome, and EZH2-based Weaver syndrome). In addition, we identified two genes, KDM3B and TYK2, which are possibly involved in genetic cancer predisposition. Conclusions: In our selected cohort of patients, pathogenic germline mutations causative or likely causative of the cancer phenotype were found in 8 patients, and two possible novel cancer-predisposing genes were identified. Therewith, our study shows the added value of sequencing beyond a cancer gene panel in selected patients, to recognize childhood cancer predisposition

High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer

Purpose: In many children with cancer and characteristics suggestive of a genetic predisposition syndrome, the genetic cause is still unknown. We studied the yield of pathogenic mutations by applying whole-exome sequencing on a selected cohort of children with cancer. Experimental Design: To identify mutations in known and novel cancer-predisposing genes, we performed trio-based whole-exome sequencing on germline DNA of 40 selected children and their parents. These children were diagnosed with cancer and had at least one of the following features: (1) intellectual disability and/or congenital anomalies, (2) multiple malignancies, (3) family history of cancer, or (4) an adult type of cancer. We first analyzed the sequence data for germline mutations in 146 known cancer-predisposing genes. If no causative mutation was found, the analysis was extended to Results: Four patients carried causative mutations in a known cancer-predisposing gene: TP53 and DICER1 (n ¼ 3). In another 4 patients, exome sequencing revealed mutations causing syndromes that might have contributed to the malignancy (EP300-based Rubinstein–Taybi syndrome, ARID1A-based Coffin–Siris syndrome, ACTB-based Baraitser–Winter syndrome, and EZH2-based Weaver syndrome). In addition, we identified two genes, KDM3B and TYK2, which are possibly involved in genetic cancer predisposition. Conclusions: In our selected cohort of patients, pathogenic germline mutations causative or likely causative of the cancer phenotype were found in 8 patients, and two possible novel cancer-predisposing genes were identified. Therewith, our study shows the added value of sequencing beyond a cancer gene panel in selected patients, to recognize childhood cancer predisposition

High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer

Purpose: In many children with cancer and characteristics suggestive of a genetic predisposition syndrome, the genetic cause is still unknown. We studied the yield of pathogenic mutations by applying whole-exome sequencing on a selected cohort of children with cancer. Experimental Design: To identify mutations in known and novel cancer-predisposing genes, we performed trio-based whole-exome sequencing on germline DNA of 40 selected children and their parents. These children were diagnosed with cancer and had at least one of the following features: (1) intellectual disability and/or congenital anomalies, (2) multiple malignancies, (3) family history of cancer, or (4) an adult type of cancer. We first analyzed the sequence data for germline mutations in 146 known cancer-predisposing genes. If no causative mutation was found, the analysis was extended to the whole exome. Results: Four patients carried causative mutations in a known cancer-predisposing gene: TP53 and DICER1 (n = 3). In another 4 patients, exome sequencing revealed mutations causing syndromes that might have contributed to the malignancy (EP300-based Rubinstein-Taybi syndrome, ARID1A-based Coffin-Siris syndrome, ACTB-based Baraitser-Winter syndrome, and EZH2-based Weaver syndrome). In addition, we identified two genes, KDM3B and TYK2, which are possibly involved in genetic cancer predisposition. Conclusions: In our selected cohort of patients, pathogenic germline mutations causative or likely causative of the cancer phenotype were found in 8 patients, and two possible novel cancer-predisposing genes were identified. Therewith, our study shows the added value of sequencing beyond a cancer gene panel in selected patients, to recognize childhood cancer predisposition. (C) 2018 AACR