scholarly journals Functional Analyses of a Novel Splice Variant in the CHD7 Gene, Found by Next Generation Sequencing, Confirm Its Pathogenicity in a Spanish Patient and Diagnose Him with CHARGE Syndrome

2018 ◽  
Vol 9 ◽  
Author(s):  
Olatz Villate ◽  
Nekane Ibarluzea ◽  
Eugenia Fraile-Bethencourt ◽  
Alberto Valenzuela ◽  
Eladio A. Velasco ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Splice Variant ◽  
Charge Syndrome ◽  
Next Generation ◽  
Spanish Patient ◽  
Chd7 Gene ◽  
Functional Analyses ◽  
Generation Sequencing

scholarly journals SUN-032 Digenic Inheritance of PCSK1 and CHD7 Mutations in PAX4 Homozygous Diabetic Male with Normosmic Hypogonadotropic Hypogonadism

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Yun Kyung Cho ◽  
Sang-Wook Kim
Keyword(s):  
Next Generation Sequencing ◽  
Hypogonadotropic Hypogonadism ◽  
Missense Mutations ◽  
Next Generation ◽  
Wild Type ◽  
Hypogonadotrophic Hypogonadism ◽  
Digenic Inheritance ◽  
Congenital Hypogonadotropic Hypogonadism ◽  
Chd7 Gene ◽  
Generation Sequencing

Abstract Background: Normosmic congenital hypogonadotropic hypogonadism denotes Kallmann syndrome not associated with anosmia or hyposmia. Over the past few years, the availability of next-generation sequencing has started to unravel the complex molecular basis of congenital hypogonadotrophic hypogonadism including digenic or oligogenic pathogenecity in addition to classic monogenic causality (1). Clinical Case: A 22-year-old male patient was referred to the endocrine clinic in 2018 with recent -onset hyperglycemia. His weight was 82.2 kg with a height of 180 cm (BMI of 25.3 kg/m2). Physical examination revealed small testes, micropenis, and no axillary and pubic terminal hair. His smell sense was intact. His hormonal test reveals low testosterone (0.10 ng/mL) and low free testosterone (0.65 pg/mL) levels with inappropriately low gonadotrophins levels. Secretion of LH and FSH increased 2-fold after GnRH stimulation. His bone age was 13-years 6-months old, and brain magnetic resonance imaging showed the presence of olfactory bulbs, and unremarkable findings except for small size of the pituitary gland. There were no signs associated with CHARGE syndrome (coloboma ocular, heart defects, atresia or stenosis of the choanae, retardation of growth and/or development, genitourinary anomalies, and ear abnormalities). Biochemical investigation demonstrated high serum glucose level and high HbA1c (13.8%). To identify variants to cause the phenotype of the proband, we adopted trio-based whole exome sequencing (WES) and candidate gene approach. Candidate genes was listed from the orphanet (https://www.orpha.net). WES of the proband revealed the presence of heterozygote missense mutations of the CHD7 gene (c.6107C>T, p.Pro2036Leu, rs369543203) and PCSK1 gene (c.239G>A, p.Arg80Gln, rs1799904). The missense variants were predicted to have a damaging effect on the encoded protein, by SIFT and PolyPhen-2 analyses. Genetic analyses of his family revealed that his father had the same heterozygote missense mutations of the CHD7 gene, but wild type of PCSK1. Proband’s mother had the same heterozygote missense mutations of PCSK1, but wild type of CHD7. Furthermore, the proband had homozygote missense mutation of PAX4 (c.575G>A, p.Arg192His, rs2233580) known as maturity-onset diabetes of the young (MODY) 9 gene. Both parents have the same but heterozygous mutation of PAX4 p.Arg192His, and pre-diabetic range of hyperglycemia. Conclusion: This is the first case demonstrating digenic inheritance of mutations in PCSK1 and CHD7 as a potential cause of normosmic hypogonadotrophic hypogonadism, interestingly in PAX4 homozygous diabetic male. Reference: (1) Maione L, et al. Genetic counseling for congenital hypogonadotropic hypogonadism and Kallmann syndrome: new challenges in the era of oligogenism and next-generation sequencing. Eur J Endocrinol. 2018;178(3):R55-R80.

scholarly journals Host_microbe_mapper allows to analyse and interpret the expression of dual RNA-seq measurements and reveals potential microbial contaminations in the data

2017 ◽  
Author(s):  
Thomas Nussbaumer
Keyword(s):  
Next Generation Sequencing ◽  
Computational Pipeline ◽  
Rna Seq ◽  
Next Generation ◽  
Sequencing Data ◽  
Link Type ◽  
Sequencing Technologies ◽  
Functional Analyses ◽  
Generation Sequencing

AbstractNext-generation sequencing technologies provide a wealth of sequencing data. To handle these data amounts, various tools were developed over the last years for mapping, normalisation and functional analyses. To support researchers in the interpretation of expression measurements originating from dual RNA-seq studies and from host-microbe systems in particular, the computational pipeline host_microbe_mapper can be applied to quantify and interpret dual RNA-seq datasets in host-microbe experiments. The pipeline with all the required scripts is stored at the Github repository (https://github.com/nthomasCUBE/hostmicrobemapper).

Labordiagnostik bei gastrointestinalen Tumoren

2020 ◽  
Vol 11 (05) ◽  
pp. 232-238
Author(s):  
Marcus Kleber
Keyword(s):  
Next Generation Sequencing ◽  
Kolorektales Karzinom ◽  
Next Generation ◽  
Generation Sequencing

ZUSAMMENFASSUNGDas kolorektale Karzinom (KRK) ist einer der häufigsten malignen Tumoren in Deutschland. Einer frühzeitigen Diagnostik kommt große Bedeutung zu. Goldstandard ist hier die Koloskopie. Die aktuelle S3-Leitlinie Kolorektales Karzinom empfiehlt zum KRK-Screening den fäkalen okkulten Bluttest. Für das Monitoring von Patienten vor und nach Tumorresektion werden die Messung des Carcinoembryonalen Antigens (CEA) und der Mikrosatellitenstabilität empfohlen. Für die Auswahl der korrekten Chemotherapie scheint derzeit eine Überprüfung des Mutationsstatus, mindestens des KRAS-Gens und des BRAF-Gens, sinnvoll zu sein. Eine Reihe an neuartigen Tumormarkern befindet sich momentan in der Entwicklung, hat jedoch noch nicht die Reife für eine mögliche Anwendung in der Routinediagnostik erreicht. Den schnellsten Weg in die breite Anwendung können Next-Generation-Sequencing-basierte genetische Tests finden.

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