p.Ser891Ala RET gene mutations in medullary thyroid cancer: Phenotypical and genealogical characterization of 28 apparently unrelated kindreds and founder effect uncovering in Northern Italy.

Hum Mutat 2019 Mar 30. Epub 2019 Mar 30.

Endocrine and Metabolic Disease Unit, Department of Medicine, ASST Spedali Civili of Brescia, Brescia, Italy.

Applying genetic screening in medullary thyroid cancer (MTC) patients we identified an unexpectedly high frequency of c.2671T>G, p.Ser891Ala RET mutation carriers. Our aim was to: (a) deeply characterize the clinical expression of this mutation, (b) identify the presence of a founder effect in our region. Genetic analysis was performed in 251 relatives from 28 Ser891Ala kindreds, among 108 p.Ser891Ala asymptomatic carriers, 64 were submitted to thyroidectomy: mean age for 10 subjects presenting C-cells hyperplasia was 30.2 ± 13.7 years, raising to 37.9 ± 10.3 in 14 subjects with micro-MTC and to 55.0 ± 14.7 years in 39 subjects with MTC. Age-related progression across histopathological groups CCH/microMTC and MTC were statistically significant: genetic screening in Ser891Ala families could be safely postponed at the age of 14. To investigate the hypothesis of a common ancestor for Ser891Ala mutation we genotyped for 18 polymorphic microsatellite markers encompassing RET locus all subjects belonging to Ser891Ala families and we identified a founder effect, estimating the age of a common ancestor, dating back to 1493 AD. Ethnographic data collected in historical archives support laboratory results; the high prevalence of this mutation in our region could suggest the hypothesis of a population study to realize a preventive intervention in a rare neoplastic disease.

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.23754DOI Listing

Still can't find the full text of the article?

We can help you send a request to the authors directly.
March 2019
12 Reads

Publication Analysis

Top Keywords

medullary thyroid
8
genetic screening
8
common ancestor
8
ser891ala families
8
thyroid cancer
8
pser891ala ret
8
progression histopathological
4
histopathological groups
4
groups cch/micromtc
4
age-related progression
4
mtc age-related
4
years subjects
4
subjects mtc
4
cch/micromtc mtc
4
mtc statistically
4
age investigate
4
families safely
4
safely postponed
4
investigate hypothesis
4
screening ser891ala
4

References

(Supplied by CrossRef)
Guidelines for diagnosis and therapy of MEN type 1 and type 2
Brandi M. L. et al.
The Journal of Clinical Endocrinology and Metabolism 2001
Multiple endocrine neoplasia 2 in Cyprus: Evidence for a founder effect
Fanis P. et al.
Journal of Endocrinological Investigation 2018

Similar Publications