Molecular characteristics

Molecular Characteristics
C12orf57 (Chromosome 12 Open Reading Frame 57) gene is located at 12p13.31 and encodes a 126-residue protein, expressed ubiquitously in human neuronal tissue with a cytoplasmic localization in neuronal cells (Akizu et al. 2013) and also expressed in multiple mouse tissues, particularly in the brain, eye, and lung.

Mutations and pathophysiology
Zahrani et al. (2013) reported a homozygous mutation in C12orf57 gene (NM_138425.2: c.1A>G; p.Met1?) in 4 individuals from one consanguineous family and a compound heterozygous mutation (NM_138425.2: c.1A>G; p.Met1?// NM_138425.2: c.152T>A; p.Leu51Gln) in an individual from another family, reportedly nonconsanguineous.

Akizu et al. (2013) reported homozygosity for the same c.1A>G mutation in 10 individuals from 4 consanguineous families. Hypotonia, moderate to severe mental retardation with features of autism, and thalamic and corpus callosum abnormalities were reported in those patients.

Platzer et al. (2015) identified a compound heterozygous mutation (NM_138425.2: c.1A>G; p.Met1?// NM_138425.2: c.184C>T; p.Gln62*) in 2 siblings born of unrelated German parents.

Recently, Alrakaf et al. (2018) reported on 23 individuals with C12orf57 mutations. The most frequent mutation encountered was the startloss p.M1?. The study reported four new variants to bring the total number of pathogenic alleles in Temtamy syndrome to seven:

  • NM_138425.2: c.-3_2delinsG (upstream of the start codon)
  • NM_ 138425.2: c .53-2A>G (abolishes a canonical splice acceptor)
  • NM_138425.2: c .43C>T; p.(Gln15*) (nonsense)
  • NM_138425.2:c.229+2T>C (abolishes a canonical splice donor)