Transient neonatal hypothyroidism in a boy with unbalanced translocation t(8;16)

Abstract

Genetic defects resulting in deficiency of thyroid hormone synthesis can be found in about 10% of the patients with permanent congenital hypothyroidism, but the identification of genetic abnormalities in association with the transient form of the disease is extremely rare. We report the case of a boy with transient neonatal hypothyroidism that was undiagnosed in the neonatal screening, associated with extrathyroid malformations and mental retardation. The boy carries an unbalanced translocation t(8;16), and his maternal uncle had a similar phenotype. Chromosomal analysis defined the patient's karyotype as 46,XY,der(8)t(8;16)(q24.3;q22)mat,16qh+. Array-CGH with patient's DNA revealed a ~80 kb terminal deletion on chromosome 8q24.3qter, and a ~21 Mb duplication on chromosome 16q22qter. ZNF252 gene, mapped to the deleted region on patient's chromosome 8, is highly expressed in the thyroid, and may be a candidate gene for our patient's transient neonatal thyroid dysfunction. This is the first report on the association of a chromosomal translocation with the transient form of congenital hypothyroidism. This description creates new hypothesis for the physiopathology of transient congenital hypothyroidism, and may also contribute to the definition of the unbalanced translocation t(8;16)(q24.3;q22) phenotype, which has never been described before.

Mutation spectrum analysis of 29 causative genes in 43 Chinese patients with congenital hypothyroidism

“…Mutations have been reported in genes controlling the biosynthetic pathway of thyroid stimulating hormone (TSH; TSHB, TRHR and IGSF1), pituitary development (POU1F1, PROP1, HESX1, LHX3, LHX4 and SOX3) (1,6) and thyroid hormone transport or action (SLC16A2/MCT8, THRB and THRA) (1). other genes (FOXI1, GLIS3, UBR1 and ZNF252P) have been reported in cases with syndromic hypothyroidism or transient cH and may be involved in cH (8)(9)(10)(11)(12)(13). These causative genes and their functions are described in Table Si. Although CH can be classified as a disease with a strong genetic component, many issues remain unresolved.…”