Data on molecular genetics published by A. Carre and colleagues
2009 JUL 28 - (NewsRx.com) -- According to recent research from Paris, France, "Thyroid transcription factor 1 (NKX2-1/TITF1) mutations cause brain-lung-thyroid syndrome, characterized by congenital hypothyroidism (CH), infant respiratory distress syndrome (IRDS) and benign hereditary chorea (BHC). The objectives of the present study were (i) detection of NKX2-1 mutations in patients with CH associated with pneumopathy and/or BHC, (ii) functional analysis of new mutations in vitro and (iii) description of the phenotypic spectrum of brain-lung-thyroid syndrome." "We identified three new heterozygous missense mutations (L176V, P202L, Q210P), a splice site mutation (376-2A -> G), and one deletion of NKX2-1 at 14q13. Functional analysis of the three missense mutations revealed loss of transactivation capacity on the human thyroglobulin enhancer/promoter. Interestingly, we showed that deficient transcriptional activity of NKX2-1-P202L was completely rescued by cotransfected PAX8-WT, whereas the synergistic effect was abolished by L176V and Q210P. The clinical spectrum of 6 own and 40 published patients with NKX2-1 mutations ranged from the complete triad of brain-lung-thyroid syndrome (50%), brain and thyroid disease (30%), to isolated BHC (13%). Thyroid morphology was normal (55%) and compensated hypothyroidism occurred in 61%. Lung disease occurred in 54% of patients (IRDS at term 76%; recurrent pulmonary infections 24%). On follow-up, 20% developed severe chronic interstitial lung disease, and 16% died," wrote A. Carre and colleagues. The researchers concluded: "We describe five new NKX2.1 mutations with, for the first time, complete rescue by PAX8 of the deficient transactivating capacity in one case. Additionally, our review shows that the majority of affected patients display neurological and/or thyroidal problems and that, although less frequent, lung disease is responsible for a considerable mortality." Carre and colleagues published their study in Human Molecular Genetics (Five new TTF1/NKX2.1 mutations in brain-lung-thyroid syndrome: rescue by PAX8 synergism in one case. Human Molecular Genetics, 2009;18(12):2266-2276). For additional information, contact M. Polak, Hopital Necker Enfants Malad, AP HP, Service Endocrinol Pediatrics, 149 Rue Sevres, F-75743 Paris 15, France. Publisher contact information for the journal Human Molecular Genetics is: Oxford University Press, Great Clarendon St., Oxford OX2 6DP, England. Keywords: France, Paris, Life Sciences, Endocrinology, Congenital Hypothyroidism, Chorea, Thyroglobulin, Pharmaceuticals, Drugs, Therapy, Treatment, Human Molecular Genetics. This article was prepared by Life Science Weekly editors from staff and other reports. Copyright 2009, Life Science Weekly via NewsRx.com.
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