Genes are listed in alphabetic order.

See Table A. Genes and Databases for chromosome locus and protein.

See Molecular Genetics for information on variants detected in this gene.

See Table 5 for common AMT and GLDC variants for which laboratories may offer targeted analysis.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

Large deletions or duplications of AMT have not been reported, but would be expected to be pathogenic due to the loss-of-function disease mechanism.

Coughlin et al [2017]

Although two individuals homozygous for a GCSH pathogenic variant were reported (as an abstract at a meeting), to date no proof of pathogenicity has been provided. No other instances of NKH caused by GCSH deficiency have been identified. The H-protein has a known role in in lipoate synthesis and could potentially affect lipoate metabolism [Mayr et al 2014]. One individual was identified with deficient H-protein enzyme activity in 1981, but this likely represented a deficiency of lipoylation. No pathogenic variant was identified in the comprehensive analysis of pathogenic variants in NKH [Kure et al 2006a, Coughlin et al 2017].