Parental α 1‐antitrypsin (PI) types and meiotic nondisjunction in the aetiology of Down syndrome

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Abstract
In 100 children with Down''s syndrome (DS), the parental origin of the supernumery chromosome 21 was investigated. In 76 cases the polymorphic regions were informative; the nondisjunction could be traced. Assessment of the .alpha.1-antitrypsin/.alpha.1-protease inhibitor (PI) types in these DS children revealed a significantly higher value of non-M PI variants (P < 0.05). In their fathers the non-M PI variants were not increased, not even in those in whom nondisjunction had taken place. A clearly significantly higher value (P .mchlt. 0.001) of non-M PI variants was found in their mothers, particularly when only the MS and MZ types which are recognized as deficiency variants were considered. Most striking is the almost 5-fold increased frequency of MS and MZ types found in mothers where the nondisjunction had occurred during the 1st meiotic division. PI deficiency may interfere with some process leading to non-disjunction. Application of Bayes'' theorem enables estimation of the risk for MZ and MS heterozygous women to have a DS child: this would be 3- to 4-fold higher than for MM homozygous women. This would be of interest for genetic counseling and enhance the benefits of prenatal diagnosis programs.