Congenital hypothyroidism (CH) affects about 1:4000 infants
and is considered one of the main causes of preventable mental
retardation in children. Universal screening of CH performed
through the Portuguese National Neonatal Screening
Programme, implemented in Portugal in 1985, has resulted in
normal development of attained children. Birth defects of the
thyroid can be divided into several groups that represent
either changes in the development of the gland or the consequences
observed in the deficient synthesis of thyroid hormones.
The defects of hormone synthesis caused by dyshor -
monogenesis occur in only 10% to 15% of cases of HC.
Defects in the thyroid peroxidase (TPO) gene are reported to
be one of the most frequent causes of CH due to dyshormonogenesis.
The aim is to review the mutational spectrum of the
TPO gene in the portuguese population through the molecular
investigation of 69 patients with permanent CH due to dys -
hormonogenesis. To complement previous results, published
in 2005, this work describes the molecular characterization of
a further fourteen children with CH and the methodology
applied. Extensive in-silico analysis was carried out for the
newly identified sequence changes as well as the formerly
published putative splicing variant. The sequence variations
identified in the TPO gene comprise ten distinct mutations
and 29 polymorphisms, enabling the determination of the
molecular etiology of CH in fifteen patients. In conclusion, it
was possible to obtain a differential diagnosis in twelve fami -
lies with CH, using a non-invasive procedure and without
interruption of medication. Identification of these and other
mutations in the TPO gene can therefore contribute considerably
towards diagnosis, a precise genetic counselling, adequate
monitoring in future pregnancies as well as putative
personalized therapies
