Molecular characteristics
TMEM231 (Transmembrane Protein 231) gene is located at 16q23.1 and encodes a protein that complexes with B9 and CC2D2A at the transition zone of cilia. This complex is involved in the formation the diffusion barrier between the cilia and plasma membrane.
Mutations and pathophysiology
Mutations in TMEM231 cause ciliopathy. Specifically, homozygous mutations in TMEM231 have been reported to cause Meckel-Gruber syndrome, while compound heterozygous mutations have been reported to cause Joubert syndrome. The clinical features of these disorders are listed in the Clinical Characteristics section.
Shaheen et al. (2013) reported homozygosity for c.751G>A mutation in TMEM231 (NM_001077416.1) leading to a frameshift and premature truncation (p.Val251Serfs*21 and p.Val251Serfs*9). The patient came from a consanguineous Arab family and displayed features consistent with Meckel-Gruber syndrome.
In another similarly affected patient born to a consanguineous Arab family, Shaheen et al. (2013) identified a homozygous c.902A>C mutation leading to a p.Gln301Pro substitution.
Srour et al. (2012) reported a compound heterozygous mutation in TMEM231: c.12T>A leading to p.Tyr4* and c.625G>A leading to p.Asp209Asn substitution. The three affected patients came from two French-Canadian families with Joubert syndrome.