High-resolution melting analysis (HRM) for mutational screening of Dnajc17 gene in patients affected by thyroid dysgenesis

Background Congenital hypothyroidism is a frequent disease occurring with an incidence of about 1/1500 newborns/year. In about 75% of the cases, CH is caused by alterations in thyroid morphogenesis, defined “thyroid dysgenesis” (TD). TD is generally a sporadic disease but in about 5% of the cases a...

Full description

Saved in:
Bibliographic Details
Published in:Journal of endocrinological investigation 2018-06, Vol.41 (6), p.711-717
Main Authors: Nettore, I. C., Desiderio, S., De Nisco, E., Cacace, V., Albano, L., Improda, N., Ungaro, P., Salerno, M., Colao, A., Macchia, P. E.
Format: Article
Language:English
Subjects:
Deoxyribonucleic acid
DNA
DNA sequencing
Endocrinology
Gene frequency
Genetic analysis
Hypothyroidism
Medicine
Medicine & Public Health
Metabolic Diseases
Morphogenesis
Mutation
Neonates
Original Article
Pax8 protein
Phenotypes
Thyroid gland
Thyroid transcription factor 1
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background Congenital hypothyroidism is a frequent disease occurring with an incidence of about 1/1500 newborns/year. In about 75% of the cases, CH is caused by alterations in thyroid morphogenesis, defined “thyroid dysgenesis” (TD). TD is generally a sporadic disease but in about 5% of the cases a genetic origin has been demonstrated. Previous studies indicate that Dnajc17 as a candidate modifier gene for hypothyroidism, since it is expressed in the thyroid bud, interacts with NKX2.1 and PAX8 and it has been associated to the hypothyroid phenotype in mice carrying a single Nkx2.1 and Pax8 genes (double heterozygous knock-out). Purpose The work evaluates the possible involvement of DNAJC17 in the pathogenesis of TD. Methods High-resolution DNA melting analysis (HRM) and direct sequencing have been used to screen for mutations in the DNAJC17 coding sequence in 89 patients with TD. Results Two mutations have been identified in the coding sequence of DNAJC17 gene, one in exon 5 (c.350A>C; rs79709714) and one in exon 9 (c.610G>C; rs117485355). The last one is a rare variant, while the rs79709714 is a polymorphism. Both are present in databases and the frequency of the alleles is not different between TD patients and controls. Conclusions DNAJC17 mutations are not frequently present in patients with TD.
ISSN:1720-8386
0391-4097
1720-8386
DOI:10.1007/s40618-017-0795-7