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Large intragenic deletion of CDC73 (exons 4-10) in a three-generation hyperparathyroidism-jaw tumor (HPT-JT) syndrome family.
- Source :
-
BMC medical genetics [BMC Med Genet] 2017 Aug 03; Vol. 18 (1), pp. 83. Date of Electronic Publication: 2017 Aug 03. - Publication Year :
- 2017
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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.<br />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.<br />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&#95;-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.<br />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.
- Subjects :
- 5' Untranslated Regions
Adenoma pathology
Adolescent
Adult
Alleles
Animals
Base Sequence
Child
DNA chemistry
DNA isolation & purification
DNA metabolism
DNA Copy Number Variations
Exons
Female
Fibroma pathology
Genetic Testing
HEK293 Cells
Humans
Hyperparathyroidism pathology
Jaw Neoplasms pathology
Leukocytes metabolism
Male
Middle Aged
Pedigree
Sequence Alignment
Tumor Suppressor Proteins metabolism
Young Adult
Adenoma genetics
Fibroma genetics
Hyperparathyroidism genetics
Jaw Neoplasms genetics
Sequence Deletion
Tumor Suppressor Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2350
- Volume :
- 18
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC medical genetics
- Publication Type :
- Academic Journal
- Accession number :
- 28774260
- Full Text :
- https://doi.org/10.1186/s12881-017-0445-0