Quaynor, SD;
Bosley, ME;
Duckworth, CG;
Porter, KR;
Kim, S-H;
Kim, H-G;
Chorich, LP;
Sullivan, ME;
Choi, J-H;
Cameron, RS;
et al.
Quaynor, SD; Bosley, ME; Duckworth, CG; Porter, KR; Kim, S-H; Kim, H-G; Chorich, LP; Sullivan, ME; Choi, J-H; Cameron, RS; Layman, LC
(2016)
Targeted next generation sequencing approach identifies eighteen new candidate genes in normosmic hypogonadotropic hypogonadism and Kallmann Syndrome.
Molecular and Cellular Endocrinology, 437.
pp. 86-96.
ISSN 0303-7207
https://doi.org/10.1016/j.mce.2016.08.007
SGUL Authors: Kim, Soo-Hyun
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Abstract
The genetic basis is unknown for ∼60% of normosmic hypogonadotropic hypogonadism (nHH)/Kallmann syndrome (KS). DNAs from (17 male and 31 female) nHH/KS patients were analyzed by targeted next generation sequencing (NGS) of 261 genes involved in hypothalamic, pituitary, and/or olfactory pathways, or suggested by chromosome rearrangements. Selected variants were subjected to Sanger DNA sequencing, the gold standard. The frequency of Sanger-confirmed variants was determined using the ExAC database. Variants were classified as likely pathogenic (frameshift, nonsense, and splice site) or predicted pathogenic (nonsynonymous missense). Two novel FGFR1 mutations were identified, as were 18 new candidate genes including: AMN1, CCKBR, CRY1, CXCR4, FGF13, GAP43, GLI3, JAG1, NOS1, MASTL, NOTCH1, NRP2, PALM2, PDE3A, PLEKHA5, RD3, and TRAPPC9, and TSPAN11. Digenic and trigenic variants were found in 8/48 (16.7%) and 1/48 (2.1%) patients, respectively. NGS with confirmation by Sanger sequencing resulted in the identification of new causative FGFR1 gene mutations and suggested 18 new candidate genes in nHH/KS.
Item Type: | Article | ||||||
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Additional Information: | © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | ||||||
Keywords: | Endocrinology & Metabolism, 06 Biological Sciences, 11 Medical And Health Sciences, 07 Agricultural And Veterinary Sciences | ||||||
SGUL Research Institute / Research Centre: | Academic Structure > Institute of Medical, Biomedical and Allied Health Education (IMBE) Academic Structure > Institute of Medical, Biomedical and Allied Health Education (IMBE) > Centre for Biomedical Education (INMEBE) |
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Journal or Publication Title: | Molecular and Cellular Endocrinology | ||||||
ISSN: | 0303-7207 | ||||||
Publisher License: | Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0 | ||||||
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URI: | https://openaccess.sgul.ac.uk/id/eprint/108161 | ||||||
Publisher's version: | https://doi.org/10.1016/j.mce.2016.08.007 |
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