Τίτλος:
HESX1 mutations are an uncommon cause of septooptic dysplasia and
hypopituitarism
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Context: Mutations in the transcription factor HESX1 have previously
been described in association with septooptic dysplasia ( SOD) as well
as isolated defects of the hypothalamic-pituitary axis.
Objective: Given that previous screening was carried out by SSCP
detection alone and limited to coding regions, we performed an in-depth
genetic analysis of HESX1 to establish the true contribution of HESX1
genetic defects to the etiology of hypopituitarism.
Design: Nonfamilial patients ( 724) with either SOD ( n = 314) or
isolated pituitary dysfunction, optic nerve hypoplasia, or midline
neurological abnormalities ( n = 410) originally screened by SSCP were
rescreened by heteroduplex detection for mutations in the coding and
regulatory regions of HESX1. In addition, direct sequencing of HESX1 was
performed in 126 patients with familial hypopituitarism from 66
unrelated families and in 11 patients born to consanguineous parents.
Patients: All patients studied had at least one of the three classical
features associated with SOD ( optic nerve hypoplasia, hypopituitarism,
midline forebrain defects).
Results: Novel sequence changes identified included a functionally
significant heterozygous mutation at a highly conserved residue ( E149K)
in a patient with isolated GH deficiency and digital abnormalities. The
overall incidence of coding region mutations within the cohort was less
than 1%.
Conclusions: Mutations within HESX1 are a rare cause of SOD and
hypopituitarism. However, the large number of familial patients with SOD
in whom no mutations were identified is suggestive of an etiological
role for other genetic factors. Furthermore, we have found that within
our cohort SOD is associated with a reduced maternal age compared with
isolated defects of the hypothalamopituitary axis.
Συγγραφείς:
McNay, David E. G.
Turton, James P.
Kelberman, Daniel
Woods,
Kathryn S.
Brauner, Raja
Papadimitriou, Anastasios
Keller,
Eberhard
Keller, Alexandra
Haufs, Nele
Krude, Heiko and
Shalet, Stephen M.
Dattani, Mehul T.
Περιοδικό:
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
DOI:
10.1210/jc.2006-1609
