title: Two novel heterozygous missense variations within the GLI2 gene in two unrelated Argentine patients.
abstract: Several heterozygous GLI2 gene mutations have been reported in patients with isolated GH deficiency (IGHD) or multiple pituitary hormone deficiency (MPHD) with or without other malformations. The primary aim of this study was to analyze the presence of GLI2 gene alterations in a cohort of patients with IGHD or MPHD and ectopic/absent posterior pituitary. The coding sequence and flanking intronic regions of GLI2 gene were amplified and directly sequenced from gDNA of 18 affected subjects and relatives. In silico tools were applied to identify the functional impact of newly found variants (Polyphen2, SIFT, Mutation Taster). We identified two novel heterozygous missense variations in two unrelated patients, p.Arg231Gln and p.Arg226Leu, located in the repressor domain of the protein. Both variations affect highly conserved amino acids of the Gli2 protein and were not found in the available databases. In silico tools suggest that these variations might be disease causing. Our study suggests that the GLI2 gene may be one of the candidate genes to analyze when an association of pituitary hormone deficiency and developmental defects in posterior pituitary gland. The highly variable phenotype found suggests the presence of additional unknown factors that could contribute to the phenotype observed in these patients.
authors: Servicio de Endocrinología, Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
authors: Matías
authors: M
authors: Juanes
authors: Servicio de Endocrinología, Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
authors: Isabel
authors: I
authors: Di Palma
authors: Servicio de Endocrinología, Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
authors: Marta
authors: M
authors: Ciaccio
authors: Servicio de Endocrinología, Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
authors: Roxana
authors: R
authors: Marino
authors: Servicio de Endocrinología, Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
authors: Pablo C
authors: PC
authors: Ramírez
authors: Servicio de Endocrinología, Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
authors: Natalia
authors: N
authors: Pérez Garrid
authors: Servicio de Endocrinología, Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
authors: Mercedes
authors: M
authors: Maceiras
authors: Servicio de Endocrinología, Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
authors: Juan M
authors: JM
authors: Lazzati
authors: Servicio de Endocrinología, Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
authors: Marco A
authors: MA
authors: Rivarola
authors: Servicio de Endocrinología, Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina. E-mail: abelgo@netizen.com.ar.
authors: Alicia
authors: A
authors: Belgorosky
mesh_terms: D001118:Argentina; D002648:Child; D002675:Child, Preschool; D005260:Female; D006579:Heterozygote; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007438:Introns; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D008831:Microcephaly / Q000175:diagnosis; D020125:Mutation, Missense; D010641:Phenotype; D010903:Pituitary Gland, Anterior / Q000002:abnormalities; D010904:Pituitary Gland, Posterior / Q000002:abnormalities; D010907:Pituitary Hormones / Q000172:deficiency*; D000075746:Zinc Finger Protein Gli2
chemical_list: D051741:Kruppel-Like Transcription Factors; D010907:Pituitary Hormones; D000075746:Zinc Finger Protein Gli2; D019382:Human Growth Hormone
keywords: GLI2 gene; IGHD; MPHD; ectopic posterior pituitary