Detection of hypopituitarism genes in Argentinean children using a next generation sequencing panel

S.A.VISHNOPOLSKA; I.BERGADA; S.CAMPER; A.KESELMAN; J.KITZMAN; M.I.PEREZ MILLAN; D.BRASLAVSKY; A. SEILICOVICH; M.A.MARTI

CABA

Congreso; Reunión conjunta de Sociedades de Biociencia; 2017

Hypopituitarism is caused by genetic and environmental factors. Over 30 genes have been implicated in isolated and combined pituitary hormone deficiency, but the majority of cases are of unknown etiology. Mutations in the PROP1 gene are the most common known cause, but the frequency of mutations in this gene varies greatly by ethnicity. The rate of mutations in PROP1 or other known hypopituitarism genes has not been analyzed in Argentinean children. We designed a custom array to assess the frequency of mutations in known genes and new candidates, based on research studies, by next generation sequencing technology.Methods: Molecular inversion probes were designed to capture 693 coding exons of 30 known genes and 37 candidate genes. We captured genomic DNA from 51 pediatric patients from Argentina with CPHD or IGHD and their relatives and conducted next generation sequencing on an Illumina platform.Results: We obtained deep coverage over targeted regions and demonstrated accurate variant detection by comparison to whole-genome sequencing in a control individual. We found a dominant mutation GH1, p.R183H, in a three-generation pedigree with isolated growth hormone deficiency. Conclusions: Molecular inversion probes capture and deep sequencing is an efficient and inexpensive method to detect mutations in patients with hypopituitarism.