Genes are listed in alphabetic order.

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

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

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; 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 quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

Probands with familial Duane syndrome described in: Miyake et al [2008], Volk et al [2010], Chan et al [2011], Miyake et al [2011], Biler et al [2017]

Probands with a family history negative for Duane syndrome described in Miyake et al [2010], Volk et al [2010], and Biler et al [2017]; however, pathogenicity of disease-associated variants was not proven for all variants.

No data on detection rate of gene-targeted deletion/duplication analysis are available; however, since CHN1 pathogenic variants act through a gain-of-function mechanism, detection of large deletions or duplication is unlikely.

Park et al [2016] studied 401 probands with Duane syndrome and found a pathogenic variant in MAFB in four probands with Duane syndrome; in three individuals the condition was familial and in the fourth the pathogenic variant was de novo. In one of the familial cases, hearing loss was present with the Duane syndrome in three of the four affected family members in three generations. In an additional ten simplex cases with Duane syndrome and hearing loss, no pathogenic variant in MAFB was identified.

Three of 77 individuals with familial Duane syndrome had a pathogenic variant in MAFB [Authors, personal observation].

Isolated Duane syndrome was observed in one of eight and one of four affected individuals in two families with a pathogenic variant in SALL4 detected on sequence analysis [Al-Baradie et al 2002, Yang et al 2013]. A study of 25 individuals with nonfamilial isolated Duane syndrome did not identify pathogenic variants on sequence analysis of SALL4 [Wabbels et al 2004].

Al-Baradie et al [2002], Kohlhase et al [2002], Kohlhase et al [2003], Borozdin et al [2004b], Kohlhase et al [2005]

Borozdin et al [2004a], Borozdin et al [2007]

Miyake et al [2008], Volk et al [2010], Chan et al [2011], Miyake et al [2011], Park et al [2016], Biler et al [2017]. In the cohort described by the authors, 98% of simplex, isolated Duane syndrome lacked an identified genetic etiology.