ClinVar

In 5 patients with Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss (EDSKSCL2; 614557) from 4 unrelated families of Austrian, Italian, French, and Turkish origin, Baumann et al. (2012) identified homozygosity for a 1-bp insertion within a 5C-nucleotide repeat in exon 3 (c.362dupC, NM_017946.2) of the FKBP14 gene, causing a frameshift predicted to result in a premature termination codon (Glu122ArgfsTer7). Western blot analysis demonstrated absence of FKBP14 in patient fibroblasts, and qRT-PCR analysis showed strongly reduced FKBP14 expression compared to controls, consistent with nonsense-mediated decay. In an unrelated patient with EDSKMH, Baumann et al. (2012) identified compound heterozygosity for the 362insC mutation and a 19-bp deletion (42_60del) in exon 1 of the FKBP14 gene (614505.0002), also predicted to result in a premature termination codon. The 362dupC mutation was linked to the same haplotype in all individuals, despite their geographically diverse origins, suggesting a possible founder event. Neither mutation was found in 200 controls of European descent.

In an 8-year-old Italian boy with EDSKSCL, Dordoni et al. (2016) identified compound heterozygosity for the recurrent c.362dupC mutation in exon 3 of the FKBP14 gene, and an in-frame 3-bp deletion (c.573_575del; 614505.0004) in exon 4, causing deletion of 1 residue (Glu191del). His unaffected parents were each heterozygous for 1 of the mutations.