The frequency and mutation rate of balanced autosomal rearrangements in man estimated from prenatal genetic studies for advanced maternal age

Abstract

The frequencies of balanced chromosome rearrangements were estimated from three series of advanced maternal-age prenatal genetic studies, and were compared to the frequencies that had been estimated from consecutive newborn surveys. In the maternal-age prenatal studies, the frequencies were: Robertsonian translocations, 0.11%; reciprocal translocations, 0.17%; and inversions, 0.12%. The total frequency of balanced rearrangements in the prenatal genetic studies performed with banding (0.40%, or 1 in 250) was twice that in the consecutive newborn surveys performed without banding (0.19%, or 1 in 526). The difference was limited to inversions and reciprocal translocations; the frequency of Robertsonian translocations was similar in the prenatal series and the newborn surveys. Both familial and de novo rearrangements were more common than anticipated. The de novo cases provided a mutation rate estimate of 4.3 per 10,000 gametes per generation (compared with 1.78 to 2.2 per 10,000 gametes in other surveys). These higher estimates may more reliably approximate the true mutation rate and frequencies of balanced rearrangements in the newborn population than do the newborn surveys.