A novel nonsense mutation in the TITF-1 gene in a Japanese family with benign hereditary chorea

作者：Nakamura Katsuya; Sekijima Yoshiki^*; Nagamatsu Kiyoshiro; Yoshida Kunihiro; Ikeda Shu ichi

来源：Journal of the Neurological Sciences, 2012, 313(1-2): 189-192.

DOI：10.1016/j.jns.2011.09.013

• Benign hereditary chorea (BHC)
• Brain-Thyroid-Lung syndrome
• Thyroid transcription factor-1 (TITF-1)
• Chorea
• Hypothyroidism
• Nkx2.1

A Japanese family with a novel nonsense mutation in the TITF-1 gene (p.Y98X) is described. The proband showed severe generalized chorea, delayed motor development, subnormal intelligence, congenital hypothyroidism, bronchial asthma, and a history of pulmonary infection, all of which are characteristic features of Brain-Thyroid-Lung syndrome. On the other hand, her brother and mother showed a mild benign hereditary chorea (BHC) phenotype with congenital hypothyroidism. Intrafamilial phenotypic variation is common in BHC/Brain-Thyroid-Lung syndrome and suggests the existence of other genetic or environmental factors regulating TITF-1 function. Although choreic movement in BHC/Brain-Thyroid-Lung syndrome is recognized as non-progressive, the proband showed re-exacerbation of choreic movement at puberty. The dopamine agonist, ropinirole hydrochloride, reduced her choreic movements, suggesting that levodopa and/or dopamine agonists may compensate for underdeveloped dopaminergic pathways in this disorder.

• 出版日期2012-2-15