AD = autosomal dominant; AR = autosomal recessive; CMA = chromosomal microarray; MOI = mode of inheritance; TCS = Treacher Collins syndrome

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.

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. Gene-targeted deletion/duplication testing will detect deletions ranging from a single exon to the whole gene; however, breakpoints of large deletions and/or deletion of adjacent genes (e.g., those described by Vincent et al [2014]) may not be detected by these methods.

Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including TCOF1 or POLR1D) that cannot be detected by sequence analysis. The ability to determine the size of the deletion/duplication depends on the type of microarray used and the density of probes in the 5q32-q33.1 or 13q12.2 regions.

Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020]

Ulhaq et al [2023]

The same homozygous variant, c.163C>G (p.Leu55Val), was reported in three families [Schaefer et al 2014, Vincent et al 2016].

Reported deletions range from single exon to whole gene [Beygo et al 2012, Bowman et al 2012, Vincent et al 2014, Vincent et al 2016]. Although >97% of reported cases had a pathogenic variant detectable by sequencing, Bowman et al [2012] reported 5% of cases (5/92) with a large deletion; therefore, the rate of large deletions may be higher than current data suggest.

Vincent et al [2016]