NA = not applicable

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

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

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.

The majority are missense variants in exon 4 leading to single amino acid substitutions in the encoded protein [Janssens et al 2000, Kinoshita et al 2000, Campos-Xavier et al 2001, Hecht et al 2001, Mumm et al 2001, Janssens et al 2003, Kinoshita et al 2004, Wallace et al 2004, Janssens et al 2006].

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 intragenic deletions or duplications have not been reported in individuals with CED.

The affected members of one family with clinical and radiographic features of CED did not share marker haplotypes at the TGFB1 locus and had no sequence alterations in TGFB1 exons 1 through 7; deletion/duplication analysis was not done on these individuals [Hecht et al 2001]. Several additional individuals with clinical and radiographic features of CED have not had TGFB1 pathogenic variants identified, implying genetic locus heterogeneity [Authors, personal observation].