ECE2018 Oral Communications Novel aspects of puberty development and Cushing's disease (5 abstracts)
Oligogenicity in Kallmann syndrome - an underestimated phenomenon?
Małgorzata Kałużna 1 , Bartłomiej Budny 1 , Michał Rabijewski 2 , Szymon Dębicki 1 , Małgorzata Trofimiuk-Muldner 3 , Agnieszka Dubiel 3 , Marek Ruchała 1 & Katarzyna Ziemnicka 1
1Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland; 2Department of Reproductive Health Center of Postgraduate Education, Warsaw, Poland; 3Nuclear Medicine Unit, Department of Endocrinology, Jagiellonian University Medical College, Krakow, Poland.
Isolated hypogonadotropic hypogonadism (IHH) is caused by impaired gonadoliberin (GnRH) gene regulation, synthesis or secretion of GnRH. Genetic factors of more than 50% of the IHH are still unknown. One the most common types of IHH is the Kallmann syndrome (KS) associated with anosmia or hyposmia. In view of technological progress and new possibilities for detecting changes in human genome a comprehensive targeted analysis using next-generation sequencing (NGS) was carried out. Screening encompassed 31 patients (27 men; 4 women) with isolated hypogonadotropic hypogonadism to search for genetic background underlying IHH. The targeted sequencing of the IHH genes was conducted on Ion Torrent Personal Genome Machine™. The panel of IHH genes (dedicated library) was constructed and designed using Ion AmpliSeq™ Designer and included coding regions for 16 genes involved in the pathogenesis of IHH (e.g. KAL1/KS1, FGFR1/KS2, PROKR2/KS3, PROK2/KS4, CHD7/KS5, FGF8/KS6, GNRHR/HH7, NELF (NSMF)/HH9, GNRH1/HH12, WDR11/HH14, HS6ST1/HH15, LRRIQ3, GLI2, OTX2, TAC3/HH10, TACR3/HH11 genes). In 25 patients (80.6%) different mutations in examined genes were found. In 13 (52%) cases monogenic mutations were identifed, whereas in 12 (48%) cases oligogenicity (alteration present in more than one IHH-associated gene in a given patient) was discovered. In the literature oligogenic inheritance is reported at the level of 10–20% of all IHH cases. Our results suggest that oligogenicity in IHH could be an underestimated phenomenon. Wide NGS analysis as a high-throughput method provide a valuable insights regarding molecular mechanisms, mutational landscape and variability of the disease.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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