0000000000395147
AUTHOR
Arndt Borkhardt
C2orf69 mutations disrupt mitochondrial function and cause a multisystem human disorder with recurring autoinflammation
BACKGROUND. Deciphering the function of the many genes previously classified as uncharacterized open reading frame (ORF) would complete our understanding of a cell’s function and its pathophysiology. METHODS. Whole-exome sequencing, yeast 2-hybrid and transcriptome analyses, and molecular characterization were performed in this study to uncover the function of the C2orf69 gene. RESULTS. We identified loss-of-function mutations in the uncharacterized C2orf69 gene in 8 individuals with brain abnormalities involving hypomyelination and microcephaly, liver dysfunction, and recurrent autoinflammation. C2orf69 contains an N-terminal signal peptide that is required and sufficient for mitochondrial…
Childhood cancer predisposition syndromes-A concise review and recommendations by the Cancer Predisposition Working Group of the Society for Pediatric Oncology and Hematology.
Heritable predisposition is an important cause of cancer in children and adolescents. Although a large number of cancer predisposition genes and their associated syndromes and malignancies have already been described, it appears likely that there are more pediatric cancer patients in whom heritable cancer predisposition syndromes have yet to be recognized. In a consensus meeting in the beginning of 2016, we convened experts in Human Genetics and Pediatric Hematology/Oncology to review the available data, to categorize the large amount of information, and to develop recommendations regarding when a cancer predisposition syndrome should be suspected in a young oncology patient. This review su…
28-year incidence and time trends of childhood leukaemia in former East Germany compared to West Germany after German reunification: A study from the German Childhood Cancer Registry
Abstract Background The aetiology of childhood leukaemia is largely unknown. Analyses of geographical differences may enhance aetiologic insights. The reunification of Germany in 1990 provides a unique opportunity to evaluate incidence patterns and time trends in two merging countries with substantial lifestyle, social and socioeconomic differences. With this study we provide an extensive assessment of 28-year incidence patterns and temporal trends after the German reunification. Methods We identified all children diagnosed with a lymphoid leukaemia (LL) or acute myeloid leukaemia (AML) before the age of 15 years between 1991 and 2018 using the German Childhood Cancer Registry (N = 14,922),…
Increasing incidence and survival of paediatric and adolescent thyroid cancer in Cyprus 1998–2017: A population-based study from the Cyprus Pediatric Oncology Registry
Paediatric and adolescent thyroid cancer incidence rates are increasing in many countries. We determined incidence rates, temporal trends and survival from thyroid cancer diagnosed in childhood and adolescence in Cyprus during 1998-2017.Patients aged 0-19 years, diagnosed with thyroid cancer in the Pediatric Oncology Registry of Cyprus were included. Crude incidence rates, age standardized rates, time trends and overall survival were analysed. Annual rates and temporal trends were calculated using Microsoft Excel 2016 and Joinpoint regression analysis.Eighty-one cases (76.5 % female, 23.5 % male) were identified. The crude rates (per 100,000 persons) were for both sexes 2.00 (95 % CI 1.61, …
A human multisystem disorder with autoinflammation, leukoencephalopathy and hepatopathy is caused by mutations in C2orf69
AbstractBackgroundDeciphering the function of the many genes previously classified as uncharacterized “open reading frame” (orf) completes our understanding of cell function and its pathophysiology.MethodsWhole-exome sequencing, yeast 2-hybrid and transcriptome analyses together with molecular characterization are used here to uncover the function of the C2orf69 gene.ResultsWe identify loss-of-function mutations in the uncharacterized C2orf69 gene in eight individuals with brain abnormalities involving hypomyelination and microcephaly, liver dysfunction and recurrent autoinflammation. C2orf69 contains an N-terminal signal peptide that is required and sufficient for mitochondrial localizatio…