Sonic Hedgehog mutations are not a common cause of congenital hypopituitarism in the absence of complex midline cerebral defects. (22nd September 2014)

• Record Type: Journal Article
• Authors: Paulo, Sabrina Soares; Fernandes‐Rosa, Fábio L.; Turatti, Wendy; Coeli‐Lacchini, Fernanda Borchers; Martinelli, Carlos E.; Nakiri, Guilherme S.; Moreira, Ayrton C.; Santos, Antônio C.; de Castro, Margaret; Antonini, Sonir R.
• Is Part Of: Clinical endocrinology. Volume 82:Number 4(2015:Apr.)
• Page Start: 562
• Page End: 569
• Publication Date: 2014-09-22
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1111/cen.12565
• Languages: English
• ISSNs: 0300-0664

Abstract

<abstract abstract-type="main" id="cen12565-abs-0001"> <title>Summary</title> <sec id="cen12565-sec-0001" sec-type="section"> <title>Context and Objective</title> <p>Sonic Hedgehog (<italic>SHH</italic>) and <italic>GLI2</italic>, an obligatory mediator of SHH signal transduction, are holoprosencephaly (HPE)‐associated genes essential in pituitary formation. <italic>GLI2</italic> variants have been found in patients with congenital hypopituitarism without complex midline cerebral defects (MCD). However, data on the occurrence of <italic>SHH</italic> mutations in these patients are limited. We screened for <italic>SHH</italic> and <italic>GLI2</italic> mutations or copy number variations (CNV) in patients with congenital hypopituitarism without MCD or with variable degrees of MCD.</p> </sec> <sec id="cen12565-sec-0002" sec-type="section"> <title>Patients and Methods</title> <p>Detailed data on clinical, laboratory and neuroimaging findings of 115 patients presenting with congenital hypopituitarism without MCD, septo‐optic dysplasia or HPE were analysed. The <italic>SHH</italic> and <italic>GLI2</italic> genes were directly sequenced, and the presence of gene CNV was analysed by multiplex ligation‐dependent probe amplification (MLPA).</p> </sec> <sec id="cen12565-sec-0003" sec-type="section"> <title>Results</title> <p>Anterior pituitary deficiency was found in 74% and 53% of patients with SOD or HPE, respectively. Diabetes insipidus was common in patients with HPE (47%) but infrequent in patients with congenital hypopituitarism or SOD (7% and 8%, respectively). A single heterozygous nonsense <italic>SHH</italic> mutation (p.Tyr175Ter) was found in a patient presenting with hypopituitarism and alobar HPE. No other SHH mutations or CNV were found. Nine <italic>GLI2</italic> variations (8 missense and 1 frameshift) including a homozygous and a compound heterozygous variation were found in patients with congenital hypopituitarism or SOD, but not in HPE patients. No <italic>GLI2</italic> CNV were found.</p> </sec> <sec id="cen12565-sec-0004" sec-type="section"> <title>Conclusion</title> <p> <italic>SHH</italic> mutations or copy number variations are not a common cause of congenital hypopituitarism in patients without complex midline cerebral defects. <italic>GLI2</italic> variants are found in some patients with congenital hypopituitarism without complex midline cerebral defects or septo‐optic dysplasia. However, functional analyses of these variants are needed to strengthen genotype–phenotype relationship.</p> </sec> </abstract>