Martin Kircher.

Whole-exome sequencing has an essential place in the evaluation of neurodevelopmental abnormalities,25,26 but it can miss somatic variants if browse depth or the alternate-allele read regularity is low, as evidenced by the fact that in our study, the TUBB2B mutation was skipped with the use of whole-exome sequencing in one participant with pachygyria. Until whole-exome sequencing with high coverage is available routinely, gene panels permit an increased depth of coverage and cost-efficient detection of somatic variants.27 Future applications of sequencing panels may allow the successful interrogation of additional disorders with known mosaicism and provide an understanding of various other disorders with high prices of de novo mutations, such as autism spectrum disorders and other neuropsychiatric disorders..Shah, M.D., M.P.H., Rodney H. Falk, M.D., Brian Claggett, Ph.D., Dalane W. Kitzman, M.D., Thomas H. Mosley, Ph.D., Kenneth R. Butler, Ph.D., Eric Boerwinkle, Ph.D., and Scott D. Solomon, M.D.: The Amyloidogenic V122I Transthyretin Variant in Elderly Black Americans Amyloid cardiovascular disease leads to an increase in ventricular wall stiffness and thickness of the heart.1 Abnormalities of transthyretin, a transport protein synthesized by the liver mainly, can lead to hereditary transthyretin-related amyloidosis.2 This disorder can be caused by any one greater than 100 stage mutations in the transthyretin gene ; the V122I variant, in which isoleucine is substituted for valine at placement 122, is the most typical mutation and occurs in 3 to 4 percent of black Americans.3-5 V122I reduces the stability of transthyretin tetramers, causing cardiac deposition of misfolded transthyretin monomers and leading to an autosomal dominant cardiomyopathy that typically occurs during or following the sixth decade of existence, with a penetrance thought to be as high as 80 percent among men.6-9 The variant has been associated with increased risks of heart death and failure.