Mutations in c12orf57 cause a syndromic form of colobomatous microphthalmia
Fatema Zahrani1, Mohammed A Aldahmesh, Muneera J Alshammari
1Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Abstract:
Microphthalmia is an important developmental eye disorder. Although mutations in several genes have been linked to this condition, they only account for a minority of cases. We performed autozygome analysis and exome sequencing on a multiplex consanguineous family in which colobomatous microphthalmia is associated with profound global developmental delay, intractable seizures, and corpus callosum abnormalities, and we identified a homozygous truncating mutation in C12orf57 [c.1A>G; p.Met1?]. In a simplex case with a similar phenotype, we identified compound heterozygosity for the same mutation and another missense mutation [c.152T>A; p.Leu51Gln]. Little is known about C12orf57 but we show that it is expressed in several mouse tissues, including the eye and brain. Our data strongly implicate mutations in C12orf57 in the pathogenesis of a clinically distinct autosomal-recessive syndromic form of colobomatous microphthalmia.
Insights
Genetic mutations in C12orf57 cause a rare, severe form of colobomatous microphthalmia, a developmental eye disorder. This condition also involves global developmental delay and seizures, highlighting a new genetic cause for syndromic microphthalmia.
Area of Science:
- Genetics
- Developmental Biology
- Ophthalmology
Background:
- Microphthalmia is a significant congenital eye disorder with known genetic causes, but many cases remain unexplained.
- Existing genetic findings account for only a fraction of microphthalmia cases, necessitating further research into novel genetic factors.
Purpose of the Study:
- To identify the genetic basis of syndromic colobomatous microphthalmia associated with global developmental delay and seizures.
- To investigate the role of the C12orf57 gene in the pathogenesis of this specific microphthalmia subtype.
Main Methods:
- Autozygome analysis and exome sequencing were employed in a multiplex consanguineous family.
- Genetic analysis was extended to a simplex case presenting with a similar phenotype.
Main Results:
- A homozygous truncating mutation (c.1A>G; p.Met1?) in C12orf57 was identified in the multiplex family.
- Compound heterozygous mutations (including c.152T>A; p.Leu51Gln) in C12orf57 were found in the simplex case.
- C12orf57 expression was confirmed in mouse eye and brain tissues, suggesting a role in development.
Conclusions:
- Mutations in C12orf57 are strongly implicated as a cause of a distinct autosomal-recessive syndromic form of colobomatous microphthalmia.
- This finding expands the genetic landscape of developmental eye disorders and associated neurological abnormalities.
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