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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Genetic diagnosis of congenital hypopituitarism by a target gene panel: novel pathogenic variants in GLI2, OTX2 and GHRHR

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Nakaguma, Marilena [1] ; Correa, Fernanda A. [1] ; Santana, Lucas S. [2] ; Benedetti, Anna F. F. [1] ; Perez, V, Ricardo ; Huayllas, Martha K. P. [3] ; Miras, Mirta B. [4] ; Funari, Mariana F. A. [1] ; Lerario, Antonio M. [5] ; Mendonca, Berenice B. [1] ; Carvalho, Luciani R. S. [1] ; Jorge, Alexander A. L. [2] ; Arnhold, Ivo J. P. [1]
Total Authors: 13
[1] Univ Sao Paulo, Hosp Clin Fac Med, Disciplina Endocrinol, Lab Hormanios & Genet Mol LIM42, Unidade Endocrino, Sao Paulo - Brazil
[2] Univ Sao Paulo, Hosp Clin Fac Med, Disciplina Endocrinol, Lab Endocrinol Celular & Mol LIM25, Unidade Endocr, Sao Paulo - Brazil
[3] Hosp Transplantes Euryclides Jesus Zerbini, Sao Paulo - Brazil
[4] Hosp Ninos Santisima Trinidad, Cordoba - Argentina
[5] Univ Michigan, Dept Internal Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 - USA
Total Affiliations: 5
Document type: Journal article
Source: ENDOCRINE CONNECTIONS; v. 8, n. 5, p. 590-595, MAY 2019.
Web of Science Citations: 0

Aim: Congenital hypopituitarism has an incidence of 1:3500-10,000 births and is defined by the impaired production of pituitary hormones. Early diagnosis has an impact on management and genetic counselling. The clinical and genetic heterogeneity of hypopituitarism poses difficulties to select the order of genes to analyse. The objective of our study is to screen hypopituitarism genes (candidate and previously related genes) simultaneously using a target gene panel in patients with congenital hypopituitarism. Methods: Screening of 117 subjects with congenital hypopituitarism for pathogenic variants in 26 genes associated with congenital hypopituitarism by massively parallel sequencing using a customized target gene panel. Results: We found three novel pathogenic variants in OTX2 c.295C>T:p.Gln99{*}, GLI2 c.1681G>T:p.Glu561{*} and GHRHR c.820\_821insC:p.Asp274Alafs{*}113, and the previously reported variants in GHRHR c.57+1G>A and PROP1 {[}c.301\_302delAG];(c.109+1G>A]. Conclusions: Our results indicate that a custom-designed panel is an efficient method to screen simultaneously variants of biological and clinical relevance for congenital GH deficiency. A genetic diagnosis was possible in 5 out of 117 (4%) patients of our cohort. We identified three novel pathogenic variants in GHRHR, OTX2 and GLI2 expanding the spectrum of variants associated with congenital hypopituitarism. (AU)

FAPESP's process: 13/03236-5 - New approaches and methodologies in molecular-genetic studies of growth and pubertal development disorders
Grantee:Alexander Augusto de Lima Jorge
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 15/26563-7 - Molecular genetic diagnosis in patients with pituitary and gonadal developmental disorders and the use of models in vitro and in vivo to evaluate the functional effect of allelic variants identified by sequencing large scale
Grantee:Luciani Renata Silveira de Carvalho
Support Opportunities: Regular Research Grants
FAPESP's process: 13/02162-8 - Molecular pathogenesis and characterization of monogenic developmental diseases: a route to translational medicine
Grantee:Berenice Bilharinho de Mendonça
Support Opportunities: Research Projects - Thematic Grants