ECE2013 Poster Presentations Pituitary – Clinical (<emphasis role="italic">Generously supported by IPSEN</emphasis>) (127 abstracts)
Report of a new case of the novel AIP p.R314W mutation in a Romanian sporadic acromegaly patient
Ionela Baciu 1 , Simona Galoiu 1, , Cristina Capatina 1, , Ileana Botusan 1, , Anda Dumitrascu 2 , Vasilie Ciubotaru 4 , Mihail Coculescu 1, , Catalina Poiana 1, & Serban Radian 1,
1Carol Davila University of Medicine, Bucharest, Romania; 2Constantin I. Parhon National Institute of Endocrinology, Bucharest, Romania; 3Department of Molecular Medicine and Surgery, Karolinska Institutet, Rolf Luft Research Center for Diabetes and Endocrinology, Stockholm, Sweden; 4Department of Neurosurgery, Bagdasar-Arseni Emergency Hospital, Bucharest, Romania; 5William Harvey Research Institute, Queen Mary University of London, London, UK.
Introduction: We have recently described a novel AIP mutation c.940C>T, p.R314W, in a young sporadic acromegaly patient.
Aim: To present a new case of AIP p.R314W mutation and screening results of a Romanian control group for p.R314W.
Patients and methods: One sporadic acromegaly patient, investigated by sequencing screening of all six AIP exons, following informed consent, as part of a sporadic pituitary adenoma cohort. 110 control subjects without clinical signs of pituitary adenoma (24M/86F) were screened for AIP exon 6 sequence changes using high resolution melting analysis of exon 6 PCR products.
Results: Sequencing of AIP revealed two heterozygous missense mutations in the acromegaly patient (female, 51 years old at diagnosis). The previously described c.940C>T, p.R314W was present together with a novel sequence change, c.878A>T, p.E293V. The patient presented a large somatotropinoma (30 mm) with perisellar invasion, optic chiasm syndrome, secondary diabetes mellitus, hypertension, and pituitary gonadotroph deficiency. Following initial transsphenoidal surgery a tumor remnant was present and required a second transsphenoidal intervention and pituitary radiotherapy for controlling tumor growth. Somatostatin analogues therapy could not achieve optimal control of GH secretion. p.R314W and p.E293V were absent 110 controls. In silico evaluation of pathogenicity (Polyphen2) of p.R314W suggested this is pathogenic, while p.E293V scored as non-pathogenic. AIP mutation screening of family members of the index case has not yet been performed.
Conclusion: We describe a novel case of AIP p.R314W mutation. This likely pathogenic mutation has been exclusively associated with sporadic acromegaly to date. Although the two reported cases are apparently unrelated, we cannot exclude a founder effect in the Romanian population. In vitro experiments are necessary for confirming the pathogenic role of this novel AIP mutation and understanding the mechanism of its deleterious effect.
Acknowledgments: This work was supported by CNCSIS TE 227/2010 grant from the Romanian Ministry of Education.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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