FMD1 = frontometaphyseal dysplasia type 1; MNS = Melnick-Needles syndrome; OPD1 = otopalatodigital syndrome type 1; OPD2 = otopalatodigital syndrome type 2; TODPD = terminal osseous dysplasia with pigmentary skin defects

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.

Robertson et al [2006b]

Robertson et al [2006a], Wade et al [2016]

All reported individuals with TODPD have been heterozygous for the synonymous change c.5217G>A, which induces a splicing abnormality that results in a loss of 48 bases from the mature transcript and predicts the deletion of 16 amino acids from the resultant FLNA protein (p.Val1724_Thr1739del) [Sun et al 2010]. This pathogenic variant appears to define this disorder.

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.

Large deletions and duplications have been associated with allelic conditions such as myxomatous cardiac valvular dystrophy (see Genetically Related Disorders), periventricular nodular heterotopia, and intellectual disability. Partial- and whole-gene deletions do not cause an X-OPD spectrum disorder phenotype.