ESPE Abstracts (2018) 89 P-P2-206

Identification of Three Novel GLI2 Gene Variants Associated with Hypopituitarism

Lidia Castro-Feijóoa, Paloma Cabanasa, Jesús Barreiroa, Paula Silvab, M Luz Coucec, Manuel Pombod & Lourdes Loidib


aUnidad de Endocrinología Pediátrica, Dpto Pediatría, Hospital Clinico Universitario de Santiago de Compostela, USC, IDIS, Santiago de Compostela, Spain; bUnidad de Medicina Molecular, Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain; cUnidad de Metabolopatías, Dpto de Pediatría, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain; dDpto de Pediatría, Universidad de Santiago de Compostela, Santiago de Compostela, Spain


GLI2 is a downstream transcription factor in Sonic Hedgehog signaling, acting early in ventral forebrain and pituitary development. Heterozygous GLI2 mutations have been reported in patients with isolated or combined pituitary hormone deficiency (CPHD).

Objective: Study of genetic etiology of the hypopituitarism and identification of the genetic alteration in GLI2 gene.

Methodology: Molecular study: Search for variants by NGS sequencing (Ion ProtonSystem, SureSelectXTCustom Agilent) in the coding region and the intronic flanking regions of a panel of genes associated with hypopituitarism and multiple hormonal deficiency. For the interpretation of variants the guidelines of the American College of Medical Genetics and Genomics were followed.

Results: We found three heterozygous GLI2 variants not previously described in 3 patients (see Table 1).

Table 1
Patient PhenotypeGLI2 gene mutationVariant interpretation
1Male with clinical and biochemical studies concordant with combined pituitary hormone deficiency (CPHD). Microgenisotomy. Postaxial polydactyly. Epilepsy and global developmental delay. Start of hormone replacement therapy in the first year of life. RNM: Absence of pituitary stalk, ectopic neurohypophysis. NM_005270.4.c.3670C>T (p.Gln1224*) (chr2:121747160). Pathogenic
2Girl with clinical and biochemical studies concordant with CPHD. Diagnosis and start of treatment was late. RNM: Absence of pituitary stalk, ectopic neurohypophysis. NM_0052270.4:C.1978G>A (p.Ala660Thr) (chr2:121743875) Probably pathogenic
3Male with clinical and biochemical studies concordant with GH deficiency. Cryptorchidism and umbilical hernia. Developmental delay. Start of GH therapy in the second year of life. RNM: Small pituitary gland, ectopic neurohypophysis. NM_005270.4:c.2059G>A (p.Gly687Arg) (chr2:121743956)Probably pathogenic

Conclusion: We had find three different variants in GLI2, described for the first time, in three patients with different phenotypes of hypopituitarism.

Article tools

My recent searches

No recent searches.