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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.)

HESX1 mutations in patients with congenital hypopituitarism: variable phenotypes with the same genotype

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Fang, Qing ; Benedetti, Anna Flavia Figueredo ; Ma, Qianyi ; Gregory, Louise ; Li, Jun Z. ; Dattani, Mehul ; Sadeghi-Nejad, Abdollah ; Arnhold, Ivo J. P. ; Mendonca, Berenice Bilharinho ; Camper, Sally A. ; Carvalho, Luciani R.
Total Authors: 11
Document type: Journal article
Source: Clinical Endocrinology; v. 85, n. 3, p. 408-414, SEP 2016.
Web of Science Citations: 11

IntroductionMutations in the transcription factor HESX1 can cause isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD) with or without septo-optic dysplasia (SOD). So far there is no clear genotype-phenotype correlation. Patients and ResultsWe report four different recessive loss-of-function mutations in three unrelated families with CPHD and no midline defects or SOD. A homozygous p.R160C mutation was found by Sanger sequencing in two siblings from a consanguineous family. These patients presented with ACTH, TSH and GH deficiencies, severe anterior pituitary hypoplasia (APH) or pituitary aplasia (PA) and normal posterior pituitary. The p.R160C mutation was previously reported in a case with SOD, CPHD and ectopic posterior pituitary (EPP). Using exome sequencing, a homozygous p.I26T mutation was found in a Brazilian patient born to consanguineous parents. This patient had evolving CPHD, normal ACTH, APH and normal posterior pituitary (NPP). A previously reported patient homozygous for p.I26T had evolving CPHD and EPP. Finally, we identified compound heterozygous mutations in HESX1, p.{[}R159W];{[}R160H], in a patient with PA and CPHD. We showed that both of these mutations abrogate the ability of HESX1 to repress PROP1-mediated transcriptional activation. A patient homozygous for p.R160H was previously reported in a patient with CPHD, EPP, APH. ConclusionThese three examples demonstrate that HESX1 mutations cause variable clinical features in patients, which suggests an influence of modifier genes or environmental factors on the phenotype. (AU)

FAPESP's process: 13/00073-8 - Molecular analysis of LHX3 gene in patients with isolated or combined deficiency of GH
Grantee:Anna Flávia Figueredo Benedetti
Support type: Scholarships in Brazil - Scientific Initiation