| Full text | |
| Author(s): |
Franca, Marcela M.
[1]
;
Jorge, Alexander A. L.
[1]
;
Carvalho, Luciani R. S.
[1]
;
Costalonga, Everlayny F.
[1]
;
Vasques, Gabriela A.
[1]
;
Leite, Claudia C.
[2]
;
Mendonca, Berenice B.
[1]
;
Arnhold, Ivo J. P.
[1]
Total Authors: 8
|
| Affiliation: | [1] Univ Sao Paulo, Unidade Endocrinol Desenvolvimento, Lab Hormonios & Genet Mol LIM 42, Disciplina Endocrinol, BR-05403900 Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Radiol, Hosp Clin, Fac Med, BR-05403900 Sao Paulo - Brazil
Total Affiliations: 2
|
| Document type: | Journal article |
| Source: | JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; v. 95, n. 11, p. E384-E391, NOV 2010. |
| Web of Science Citations: | 55 |
| Abstract | |
Context: GLI2 is a transcription factor downstream in Sonic Hedgehog signaling, acting early in ventral forebrain and pituitary development. GLI2 mutations were reported in patients with holoprosencephaly (HPE) and pituitary abnormalities. Objective: The aim was to report three novel frameshift/nonsense GLI2 mutations and the phenotypic variability in the three families. Setting: The study was conducted at a university hospital. Patients and Methods: The GLI2 coding region of patients with isolated GH deficiency (IGHD) or combined pituitary hormone deficiency was amplified by PCR using intronic primers and sequenced. Results: Three novel heterozygous GLI2 mutations were identified: c. 2362\_2368del p. L788fsX794 (family 1), c. 2081\_2084del p. L694fsX722 (family 2), and c. 1138 G > T p. E380X (family 3). All predict a truncated protein with loss of the C-terminal activator domain. The index case of family 1 had polydactyly, hypoglycemia, and seizures, and GH, TSH, prolactin, ACTH, LH, and FSH deficiencies. Her mother and seven relatives harboring the same mutation had polydactyly, including two uncles with IGHD and one cousin with GH, TSH, LH, and FSH deficiencies. In family 2, a boy had cryptorchidism, cleft lip and palate, and GH deficiency. In family 3, a girl had hypoglycemia, seizures, excessive thirst and polyuria, and GH, ACTH, TSH, and antidiuretic hormone deficiencies. Magnetic resonance imaging of four patients with GLI2 mutations and hypopituitarism showed a hypoplastic anterior pituitary and an ectopic posterior pituitary lobe without HPE. Conclusion: We describe three novel heterozygous frameshift or nonsense GLI2 mutations, predicting truncated proteins lacking the activator domain, associated with IGHD or combined pituitary hormone deficiency and ectopic posterior pituitary lobe without HPE. These phenotypes support partial penetrance, variable polydactyly, midline facial defects, and pituitary hormone deficiencies, including diabetes insipidus, conferred by heterozygous frameshift or nonsense GLI2 mutations. (J Clin Endocrinol Metab 95: E384-E391, 2010) (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 |