Kenny-Caffey Syndrome Type 1 via the TBCE Gene

Kenny-Caffey syndrome is classified into two types in terms of clinical phenotypes and corresponding genetic defects. Kenny‑Caffey syndrome Type 1 is an autosomal recessive disorder characterized by growth retardation, thickening of the long bones, medullary stenosis (thin marrow cavities), dysmorphic features, and recurrent hypocalcemia due to hypoparathyroidism (Parvari et al. 2002). To date, this disease has been observed almost exclusively in the Middle East. Hypoparathyroidism-retardation-dysmorphism syndrome (HRD; also known as Sanjad-Sakati syndrome) is an allelic form of Kenny‑Caffey syndrome Type 1.

Kenny-Caffey syndrome Type 1 is an autosomal recessive disorder caused by TBCE variants (Parvari et al. 2002). The TBCE gene (17 coding exons) encodes tubulin-folding cofactor E, a chaperone protein required for the proper folding of alpha-tubulin subunits and the formation of alpha-beta-tubulin heterodimers. TBCE pathogenic variants also cause HRD. Genetic defects documented to date in TBCE include a nonsense variant and small deletions (Human Gene Mutation Database).

The mutation detection rate of TBCE in a large cohort of patients with Kenny-Caffey syndrome Type 1 is unknown in the literature because mutations have been reported only in limited cases. Analytical sensitivity should be high as the reported pathogenic variants are detectable by sequencing.

No large deletions or duplications have been reported in TBCE.

This test provides full coverage of all coding exons of the TBCE gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).