Mosaicism in Stickler syndrome

Area of Science:

• Genetics
• Molecular Biology
• Medical Genetics

Background:

• Stickler syndrome is a group of inherited disorders affecting connective tissues.
• Mutations in COL2A1, COL11A1, COL11A2, and COL9A1 are known causes of Stickler syndrome.
• Non-penetrance and mosaicism for COL2A1 mutations have not been previously reported in Stickler syndrome.

Observation:

• A family with two clinically affected siblings with Stickler syndrome and unaffected parents was studied.
• Both affected siblings carried a novel heterozygous mutation in exon 26 of COL2A1 (c.1525delT).
• This mutation leads to a premature termination codon, impacting collagen II synthesis.

Findings:

• Low-level mosaicism for the identified COL2A1 mutation was detected in DNA from one parent's whole blood.
• This represents the first reported instance of mosaicism for a COL2A1 mutation in Stickler syndrome.
• The affected siblings inherited the mutation, while the parent showed subclinical mosaicism.

Implications:

• The findings suggest that parental molecular testing should be considered in cases of Stickler syndrome with seemingly unaffected parents.
• Identifying parental mosaicism is crucial for accurate genetic counseling regarding recurrence risks.
• Screening for mild, age-related manifestations may be beneficial in parents with detected mosaicism.