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A novel NKX2.1 mutation in a family with hypothyroidism and benign hereditary chorea.

Authors: Ferrara, AM  De Michele, G  Salvatore, E  Di Maio, L  Zampella, E  Capuano, S  Del Prete, G  Rossi, G  Fenzi, G  Filla, A  Macchia, PE 
Citation: Ferrara AM, etal., Thyroid. 2008 Sep;18(9):1005-9. doi: 10.1089/thy.2008.0085.
Pubmed: (View Article at PubMed) PMID:18788921
DOI: Full-text: DOI:10.1089/thy.2008.0085

BACKGROUND: We studied a boy with congenital hypothyroidism, benign hereditary chorea, and respiratory distress. His mother and his grandfather were affected by hypothyroidism with a late onset and benign hereditary chorea. The aim of this study was to establish the genetic defects that cause that phenotype and study the molecular mechanisms of the pathology. METHODS: NKX2.1, PAX8, NKX2.5, and TAZ genes were sequenced. RESULTS: Direct sequencing of the NKX2.1 gene showed, in all the affected, a new heterozygous mutation from cytosine to adenine in the second base of the triplet encoding for the amino acid at position 145. The mutation (C609A) is responsible for a change from serine to a stop codon (S145X). We also demonstrated that the mutant protein is predominantly in the cytoplasm and unable to translocate into the nucleus. Of note, the S145X mutation produces variable phenotypes in the affected members of the family. No mutations have been identified in the NKX2.5, PAX8, and TAZ genes. CONCLUSIONS: Our study extends the knowledge of the functional effect of NKX2.1 mutations and further highlights the complexities of genotype-phenotype correlation in the NKX2.1 deficiency syndromes.


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RGD Object Information
RGD ID: 11073166
Created: 2016-04-28
Species: All species
Last Modified: 2016-04-28
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.