Molecular characteristics
The POC1A geneis located at 3p21.2 andencodes POC1A and POC1B. They consist of two domains separated by a spacer sequence, the N-terminal WD40 domain. Both POC1 proteins localize to the attachment points of multiple distinct fiber systems that contact the centriole/basal body centriole via their WD40 domain and appear to play a role in centriole duplication and/or maintenance. Shaheen et al. (2012) performed POC1A-knockdown experiments in fibroblast cells using RNAi and demonstrated that POC1A deficiency causes a severe ciliogenesis defect.
Mutations and pathophysiology
Cells with POC1A mutations have an increase in the frequency of centrosomal amplification and multipolar spindle formation compared to control cells and have abnormal mitotic mechanics and impaired ciliogenesis. Additionally, the centrosomal disorganization and increase in centrosome number are associated with abnormal trafficking from the plasma membrane to the Golgi.
The following are selected examples of the pathogenic variants in POC1A leading to SOFT syndrome as reported in literature:
- Shamseldin et al. (2012) identified homozygosity for a premature nonsense mutation, c.241C>T (p.Arg81*) in three families with primordial dwarfism and distinctive facial dysmorphism.
- Sarig et al. (2012) reported a homozygous missense mutation, c.512T>C (p.Leu171Pro) in two families.
- Koparir et al. (2015) reported a homozygous missense mutation in exon 4 causing a p.T120A in two individuals from one family.
- Chen et al. (2015) reported a single nucleotide deletion, c.1048delC (p.Q250Rfs*4) in one individual.
- Barraza‐García et al. (2015) reported two premature truncating mutations, c.254delT (p.Leu85Alafs*22) and 515G>A (p.Trp172*) in two families.
- Anazi et al. (2017) reported homozygosity for c.241C>T (p.Arg81*).