Ectrodactyly and lethal pulmonary acinar dysplasia associated with homozygous FGFR2 mutations identified by exome sequencing

First published: 11 July 2016Abstract not availableChristopher P. Barnett, Nathalie J. Nataren, Manuela Klingler-Hoffmann, Quenten Schwarz, Chan-Eng Chong, Young K. Lee, Damien L. Bruno, Jill Lipsett, Andrew J. McPhee, Andreas W. Schreiber, Jinghua Feng, Christopher N. Hahn, and Hamish S. Scot

Bromatological analysis of annatto (Bixa orellana L.) seeds

Objective: to carry out a bromatological and physicochemical analysis of local annatto seeds and a commercial paste. Materials and Methods: local annatto seeds to which a physicochemical analysis was carried out where ash, humidity (weight difference), dry matter, proteins were determined. ADF and NDF, fat, and in addition, bromatological analysis was carried out on the samples and the commercial pasta. Results: sample M3 (dark heart-shaped annatto without filaments) presented the highest values. The bixin content was recorded with 4.09% in sample M2 (heart-shaped red annatto without filaments) and the commercial paste was the lowest with 0.56%. Limitations and Implications of the study: the importance of performing the bromatological and physicalchemical analysis of annatto seeds of local genotypes determined which of the local samples and the commercial paste are the ones that contain the greatest amount of bixin. Findings and Conclusions: Sample M3 (dark heart-shaped annatto without filaments) presented the highest values. The highest bixin content was found in the smooth heart-red variety and the lowest value in the commercial pasta

Allan-Herndon-Dudley syndrome with unusual profound sensorineural hearing loss

The Allan–Herndon–Dudley syndrome is caused by mutations in the thyroid hormone transporter, Monocarboxylate transporter 8 (MCT8). It is characterized by profound intellectual disability and abnormal thyroid function. We report on a patient with Allan–Herndon–Dudley syndrome (AHDS) with profound sensorineural hearing loss which is not usually a feature of AHDS and which may have been due to a coexisting nonsense mutation in Microphthalmia-associated transcription factor (MITF)

Integrative genomic analysis reveals cancer-associated mutations at diagnosis of CML in patients with high-risk disease

Genomic events associated with poor outcome in chronic myeloid leukemia (CML) are poorly understood. We performed whole-exome sequencing, copy-number variation, and/or RNA sequencing for 65 patients to discover mutations at diagnosis and blast crisis (BC). Forty-six patients with chronic-phase disease with the extremes of outcome were studied at diagnosis. Cancer gene variants were detected in 15 (56%) of 27 patients with subsequent BC or poor outcome and in 3 (16%) of 19 optimal responders (P = .007). Frequently mutated genes at diagnosis were ASXL1, IKZF1, and RUNX1 The methyltransferase SETD1B was a novel recurrently mutated gene. A novel class of variant associated with the Philadelphia (Ph) translocation was detected at diagnosis in 11 (24%) of 46 patients comprising fusions and/or rearrangement of genes on the translocated chromosomes, with evidence of fragmentation, inversion, and imperfect sequence reassembly. These were more frequent at diagnosis in patients with poor outcome: 9 (33%) of 27 vs 2 (11%) of 19 optimal responders (P = .07). Thirty-nine patients were tested at BC, and all had cancer gene variants, including ABL1 kinase domain mutations in 58%. However, ABL1 mutations cooccurred with other mutated cancer genes in 89% of cases, and these predated ABL1 mutations in 62% of evaluable patients. Gene fusions not associated with the Ph translocation occurred in 42% of patients at BC and commonly involved fusion partners that were known cancer genes (78%). Genomic analysis revealed numerous relevant variants at diagnosis in patients with poor outcome and all patients at BC. Future refined biomarker testing of specific variants will likely provide prognostic information to facilitate a risk-adapted therapeutic approach.Susan Branford … David T. Yeung … Naranie Shanmuganathan … Christopher Hahn … Deborah L. White, Agnes S.M. Yong, David M. Ross, Hamish S. Scott, Andreas W. Schreiber, and Timothy P. Hughe