RESUMEN
Myeloproliferative neoplasms (MPNs) driver mutations are usually found in JAK2, MPL, and CALR genes; however, 10%-15% of cases are triple negative (TN). A previous study showed lower rate of JAK2 V617F in primary myelofibrosis patients exposed to low doses of ionizing radiation (IR) from Chernobyl accident. To examine distinct driver mutations, we enrolled 281 Ukrainian IR-exposed and unexposed MPN patients. Genomic DNA was obtained from peripheral blood leukocytes. JAK2 V617F, MPL W515, types 1- and 2-like CALR mutations were identified by Sanger Sequencing and real time polymerase chain reaction. Chromosomal alterations were assessed by oligo-SNP microarray platform. Additional genetic variants were identified by whole exome and targeted sequencing. Statistical significance was evaluated by Fisher's exact test and Wilcoxon's rank sum test (R, version 3.4.2). IR-exposed MPN patients exhibited a different genetic profile vs unexposed: lower rate of JAK2 V617F (58.4% vs 75.4%, P = .0077), higher rate of type 1-like CALR mutation (12.2% vs 3.1%, P = .0056), higher rate of TN cases (27.8% vs 16.2%, P = .0366), higher rate of potentially pathogenic sequence variants (mean numbers: 4.8 vs 3.1, P = .0242). Furthermore, we identified several potential drivers specific to IR-exposed TN MPN patients: ATM p.S1691R with copy-neutral loss of heterozygosity at 11q; EZH2 p.D659G at 7q and SUZ12 p.V71 M at 17q with copy number loss. Thus, IR-exposed MPN patients represent a group with distinct genomic characteristics worthy of further study.
Asunto(s)
Accidente Nuclear de Chernóbil , Trastornos Mieloproliferativos/etiología , Neoplasias Inducidas por Radiación/etiología , Contaminantes Radiactivos/efectos adversos , Adulto , Anciano , Calreticulina/genética , Aberraciones Cromosómicas , ADN/genética , Femenino , Dosificación de Gen , Humanos , Janus Quinasa 2/genética , Pérdida de Heterocigocidad , Masculino , Persona de Mediana Edad , Mutación Missense , Trastornos Mieloproliferativos/epidemiología , Trastornos Mieloproliferativos/genética , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias Inducidas por Radiación/genética , Receptores de Trombopoyetina/genética , Ucrania/epidemiología , Secuenciación del Exoma , Adulto JovenRESUMEN
BACKGROUND: There is limited data on gastric emptying in dyspeptic children. We aimed to determine solid and liquid emptying rates in dyspeptic children and correlate with clinical characteristics. METHODS: Charts of dyspeptic children undergoing 4-hour dual-phase gastric scintigraphy were reviewed for demographics, symptoms, and comorbidities. KEY RESULTS: In 1078 dyspeptic patients (65% females, median age 13 years) vomiting (55%), nausea (53%), and abdominal pain (52%) were the most common symptoms. The most common comorbidities were mental health (32%), neurologic (27%), and hypermobility spectrum disorders (20%). Solid and liquid emptying rates were aligned in 61.23%. Delayed solid with normal liquid emptying were noted in 2.5%, compared to delayed liquid with normal solid emptying in 26.16%. Abdominal pain had a trend for association with delayed or normal solid emptying (p = 0.06). Nausea was mostly reported with normal solid emptying (p < 0.0001) and underreported in patients <12 years with vomiting (29%). Abnormal solid emptying (rapid and delayed) was noted more frequently in children with mental health disorders (p = 0.027). Rapid liquid emptying was more common in children with genetic disorders (p = 0.032). CONCLUSION AND INFERENCES: Over half of children with dyspepsia had delayed liquid gastric emptying, and one quarter had delayed liquid with normal solid emptying. Dual-phase gastric emptying studies may help target therapy in dyspeptic children. Nausea is not a reliable symptom for dyspepsia in younger children. Given the significant association of abnormal gastric emptying in children with mental health disorders, we recommend screening and treating children with dyspepsia.