Novel truncating germline variant reinforces TINF2 as a susceptibility gene for familial non-medullary thyroid cancer.
J Med Genet
; 61(10): 939-942, 2024 Sep 24.
Article
in En
| MEDLINE
| ID: mdl-39103207
ABSTRACT
BACKGROUND:
It has long been observed that there are families in which non-medullary thyroid cancer (NMTC) occurs, but few syndromes and genes have been described to date. Proteins in the shelterin complex have been implied in cancer. Here, we have studied shelterin genes in families affected by NMTC (FNMTC).METHODS:
We performed whole-exome sequencing (WES) in 10 affected individuals from four families with at least three affected members. Polymerase chain reaction (PCR) and Sanger sequencing were performed to search for variants in the TINF2 gene in 40 FNMTC families. TINF2 transcripts and loss of heterozygosity (LOH) were studied in several affected patients of one family.RESULTS:
We found the c.507G>T variant in heterozygosis in the TINF2 gene in one family, co-segregating in all five affected members. This variant affects the normal splicing. LOH was not observed.CONCLUSIONS:
Our results reinforce the TINF2 gene as a susceptibility cause of FNMTC suggesting the importance of location of frameshift variants in TINF2. According to our data and previous literature, TINF2 pathogenic variants appear to be a significant risk factor for the development of NMTC and/or melanoma.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pedigree
/
Thyroid Neoplasms
/
Germ-Line Mutation
/
Genetic Predisposition to Disease
/
Exome Sequencing
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
J Med Genet
Year:
2024
Document type:
Article
Affiliation country:
Spain
Country of publication:
United kingdom