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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.)

Relatively high frequency of non-synonymous GLI2 variants in patients with congenital hypopituitarism without holoprosencephaly

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Author(s):
Franca, Marcela M. [1] ; Jorge, Alexander A. L. [1] ; Carvalho, Luciani R. S. [1] ; Costalonga, Everlayny F. [1] ; Otto, Aline P. [1] ; Correa, Fernanda A. [1] ; Mendonca, Berenice B. [1] ; Arnhold, Ivo J. P. [1]
Total Authors: 8
Affiliation:
[1] Univ Sao Paulo, Fac Med, Lab Hormonios & Genet Mol LIM 42, Hosp Clin, Unidade Endocrinol Desenvolvimento, Disciplina End, Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: CLINICAL ENDOCRINOLOGY; v. 78, n. 4, p. 551-557, APR 2013.
Web of Science Citations: 20
Abstract

Objective GLI2 is a downstream transcription factor in Sonic Hedgehog signalling, acting early in ventral forebrain and pituitary development. Heterozygous nonsense GLI2 mutations have been reported in patients with isolated or combined pituitary hormone deficiency (CPHD), with or without holoprosencephaly. The aim of this study was to screen for GLI2 mutations in a large cohort of patients with congenital GH deficiency. Design and Patients The GLI2 coding region of 41 patients with severe isolated GH deficiency (IGHD) and 136 patients with CPHD was amplified by PCR using intronic primers and sequenced. The frequency of GLI2 variants was verified in up to 155 Brazilian controls and in the 1000 Genomes database. The consequences of allelic variants were analysed by the Polyphen, SIFT, Mutationtaster and SNAP prediction sites. Results Eighteen different heterozygous non-synonymous GLI2 variants were identified in 24 patients. Twenty-three patients had CPHD and one had IGHD. Two patients had additional diabetes insipidus, indicating deficiencies of anterior and posterior pituitary lobes. The posterior pituitary lobe on MRI was ectopic in 16, not visible in 4, normally placed in 2 and imaging was not available in two patients, but there were no signs of holoprosencephaly. Sixteen GLI2 variants were considered deleterious in at least one of the prediction sites. Conclusions A relatively high frequency of non-synonymous GLI2 variants was identified in patients with congenital GH deficiency without other brain defects, and most of these patients presented with CPHD and an ectopic posterior pituitary lobe. In vitro functional assays may contribute to ascertain the deleterious consequences of these variants. (AU)

FAPESP's process: 05/04726-0 - Molecular characterization of congenital endocrine diseases that affect growth and development
Grantee:Ana Claudia Latronico Xavier
Support Opportunities: Research Projects - Thematic Grants