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Research Letter |

Expanding Phenotypic Spectrum of NKX2-1–Related Disorders—Mitochondrial and Immunologic Dysfunction

Elizabeth A. Coon, MD1; J. Eric Ahlskog, PhD, MD1; Marc C. Patterson, MD1; Zhiyv Niu, PhD2; Margherita Milone, MD, PhD1
[+] Author Affiliations
1Department of Neurology, Mayo Clinic, Rochester, Minnesota
2Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
JAMA Neurol. 2016;73(2):237-238. doi:10.1001/jamaneurol.2015.2976.
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This case series describes 2 members of a family who had a novel NKX2-1 mutation associated with reduction of muscle mitochondrial respiratory chain complex activity and recurrent meningitis.

Autosomal dominant NKX2-1–related disorders present with a spectrum of manifestations that includes benign hereditary chorea, hypothyroidism, and pulmonary dysfunction (brain-lung-thyroid syndrome).1,2 Multisystem involvement varies substantially,3 likely stemming from the mutated protein’s function. NKX2-1 is a transcription factor expressed during development of the central nervous system, especially the basal ganglia and hypothalamus, thyroid, and lung.4

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Pedigree and Results of Molecular Analysis

The pedigree is shown in A. B, The chromatogram demonstrates a C>T in exon 3 of NKX2-1, resulting in p.Arg243Cys. The mutated arginine is in the homeobox domain, highly conserved across species, and predicted to be deleterious.

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