Molecular analysis of the PAX8 gene in a sample of Mexican patients with primary congenital hypothyroidism: identification of the recurrent p.Arg31His mutation.

摘要

The Mexican population has one of the highest recorded incidences of primary congenital hypothyroidism (CH) in the world (i.e. 8-3/10 000 live births in South-east Mexico). However, it is not known whether mutations in genes involved in thyroid gland development, such as PAX8 (paired box gene 8), contribute to this high frequency of CH. The aim of this study was to ascertain whether mutations in the PAX8 gene are associated with CH in 100 sporadic and unrelated patients of Mexican origin detected through neonatal TSH (thyroid-stimulating hormone) screening and with a confirmed diagnosis of permanent primary CH. In most cases (n = 96), the diagnosis of thyroid dysgenesis (TD) was established by ~(99m)Tc scintigraphy. In each patient, the entire PAX8 coding sequence (RefSeq NM_ 003466.3), including exon-intron boundaries, was analysed by single-stranded conformation polymorphism analysis and direct sequencing. Potential deleterious splicing effects caused by disruption of exonic splicing enhancers (ESEs) were established by assessing all silent and unreported exonic variations identified in CH cases using ESEfinder ver. 3.0 software (http://rulai.cshl.edu/ cgi-bin/tools/ESE3/esefinder.cgi?process=home). The unreported variations in the PAX8 gene were tested in DNA samples of 200 healthy Mexican individuals.