Mutation in CDKN1B 3[prime]-UTR region in a patient with acromegaly and primary hyperparathyroidism

Elizaveta Mamedova; Natalia Mokrysheva; Ekaterina Pigarova; Elena Przhiyalkovskaya; Evgeniy Vasiliev; Lyudmila Rozhinskaya; Anatoliy Tiulpakov

doi:10.1530/endoabs.37.EP1091

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Endocrine Abstracts (2015) 37 EP1091 | DOI: 10.1530/endoabs.37.EP1091

ECE2015 Eposter Presentations Endocrine tumours (69 abstracts)

Mutation in CDKN1B 3′-UTR region in a patient with acromegaly and primary hyperparathyroidism

Elizaveta Mamedova , Natalia Mokrysheva , Ekaterina Pigarova , Elena Przhiyalkovskaya , Evgeniy Vasiliev , Lyudmila Rozhinskaya & Anatoliy Tiulpakov

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Endocrinology Research Center, Moscow, Russia.

Introduction: Multiple endocrine neoplasia type 4 (MEN4) is a rare disorder, caused by inactivating mutations in CDKN1B gene that encodes p27^kip1 cyclin-dependent kinase inhibitor. To date nine different germline CDKN1B mutations have been described in patients with clinical features of multiple endocrine neoplasia type 1 (MEN1) negative for MEN1 mutations (MEN1 phenocopies).

Case report: We present a female 54 y.o. with clinical features of MEN1: active acromegaly due to GH-producing pituitary macroadenoma after two consecutive neurosurgical interventions (transcranial and transsphenoidal) with remaining tissue in left cavernous sinus, requiring treatment with long-acting somatostatin analogues; mild primary hyperparathyroidism with ultrasound signs of superior right parathyroid adenoma; multinodular colloid goiter; extirpation of uterus and ovaries for adenomatous endometrial polyp, multinodular fibromyoma and endometrioid cyst; right mammary gland resection for benign lesion. Genetic testing for MEN1 germline mutation was negative. Genomic DNA from a blood sample of this patient together with ten other MEN1 phenocopies underwent high-throughput sequencing on the Ion Torrent Personal Genome Machine (Life Technologies) using a custom-designed AmpliSeq panel for the sequencing of a variety of genes, including CDKN1B, which could be responsible for the development of MEN1 phenocopies. We revealed a heterozygous mutation in 3′-UTR g.3897G>T (c×8G>T) in CDKN1B gene, which was in silico tested with free web-based application for disease-causing potential of DNA sequence alterations MutationTaster, detecting splice site alterations. Further in vitro studies are needed to confirm, whether this mutation alters protein function.

Conclusions: To our knowledge, we describe the first mutation in 3′-UTR of CDKN1B in a patient with MEN1 phenocopy.

Disclosure: This work was supported by the Grant of the President of the Russian Federation for young PhD scientists (awarded to E G Przyjalkowski : grant Number: MK-5411.2014.7).