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BMC Med Genet. 2017 Aug 3;18(1):83. doi: 10.1186/s12881-017-0445-0.

Large intragenic deletion of CDC73 (exons 4-10) in a three-generation hyperparathyroidism-jaw tumor (HPT-JT) syndrome family.

Author information

1
Medical Genetics, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy. v.guarnieri@operapadrepio.it.
2
Department of Otolaryngology - Head and Neck Surgery, University of Toronto, Toronto, ON, Canada.
3
Department of Medicine, University of Toronto, Toronto, ON, Canada.
4
Division of Endocrinology, Women's College Hospital, Toronto, ON, Canada.
5
Department of Otolaryngology, Head & Neck Surgery, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
6
Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
7
Departments of Laboratory Medicine and Pathobiology, Medicine and Genetics, University of Toronto, Toronto, ON, Canada.
8
Medical Genetics, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy.
9
Endocrinology, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy.
10
Metabolic Disorders and Complications, McGill University Health Centre-Research Institute, Montreal, QC, Canada.
11
Departments of Medicine, Physiology and Human Genetics, McGill University, Montreal, QC, Canada.

Abstract

BACKGROUND:

Inactivating mutations of CDC73 cause Hyperparathyroidism-Jaw Tumour syndrome (HPT-JT), Familial Isolated Hyperparathyroidism (FIHP) and sporadic parathyroid carcinoma. We conducted CDC73 mutation analysis in an HPT-JT family and confirm carrier status of the proband's daughter.

METHODS:

The proband had primary hyperparathyroidism (parathyroid carcinoma) and uterine leiomyomata. Her father and daughter had hyperparathyroidism (parathyroid adenoma) but no other manifestations of HPT-JT. CDC73 mutation analysis (sequencing of all 17 exons) and whole-genome copy number variation (CNV) analysis was done on leukocyte DNA of the three affecteds as well as the proband's unaffected sister.

RESULTS:

A novel deletion of exons 4 to 10 of CDC73 was detected by CNV analysis in the three affecteds. A novel insertion in the 5'UTR (c.-4_-11insG) that co-segregated with the deletion was identified. By in vitro assay the 5'UTR insertion was shown to significantly impair the expression of the parafibromin protein. Screening for the mutated CDC73 confirmed carrier status in the proband's daughter and the biochemistry and ultrasonography led to pre-emptive surgery and resolution of the hyperparathyroidism.

CONCLUSIONS:

A novel gross deletion mutation in CDC73 was identified in a three-generation HPT-JT family emphasizing the importance of including screening for large deletions in the molecular diagnostic protocol.

KEYWORDS:

CDC73; Germline; HPT-JT syndrome; Parathyroid carcinoma

PMID:
28774260
PMCID:
PMC5543551
DOI:
10.1186/s12881-017-0445-0
[Indexed for MEDLINE]
Free PMC Article

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