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Risk of dominant mutation in older fathers: evidence from osteogenesis imperfecta
Abstract:
The mean paternal age at birth of 80 presumed mutant cases of dominant osteogenesis imperfecta (OI) was significantly higher than that of population controls and remained so after adjusting for maternal age. There was also an increase in mean maternal age (not significant) which disappeared after adjusting for paternal age. No significant increase in maternal or paternal age was found in cases having OI either of a dominant type with an affected parent or of a type (Sillence type III) usually regarded as recessive. We conclude that, as in certain other dominant conditions, the risk of mutant OI increases with paternal age. However, the rate of increase of risk with paternal age appears to be considerably lower than, for example, in achondroplasia. The overall risk of fresh dominant mutation in older fathers may therefore be lower than has previously been suggested.
Insights
Advanced paternal age increases the risk of dominant osteogenesis imperfecta (OI) mutations. However, the increased risk appears lower than in other conditions like achondroplasia.
Area of Science:
- Genetics
- Reproductive Medicine
- Pediatrics
Background:
- Osteogenesis imperfecta (OI) is a group of genetic disorders characterized by fragile bones.
- Dominant forms of OI are often caused by new mutations.
- Paternal age has been linked to increased mutation rates in other genetic disorders.
Purpose of the Study:
- To investigate the association between parental age and the occurrence of new dominant mutations in osteogenesis imperfecta.
- To compare the effect of paternal age on OI mutation risk with other known genetic conditions.
Main Methods:
- Retrospective case-control study.
- Comparison of mean paternal and maternal ages at birth between 80 presumed mutant cases of dominant OI and population controls.
- Statistical adjustment for maternal age when analyzing paternal age effects.
Main Results:
- Mean paternal age was significantly higher in dominant OI cases compared to controls, even after adjusting for maternal age.
- Mean maternal age was not significantly higher in cases and this effect disappeared after adjusting for paternal age.
- No significant age effect was observed in OI cases with an affected parent or in Sillence type III OI.
Conclusions:
- Paternal age is a significant risk factor for new dominant mutations causing osteogenesis imperfecta.
- The rate of risk increase with paternal age for OI appears lower than for achondroplasia.
- The overall risk of fresh dominant mutations in older fathers may be lower than previously estimated.