Parental α 1‐antitrypsin (PI) types and meiotic nondisjunction in the aetiology of Down syndrome
- 1 October 1981
- journal article
- Published by Wiley in Clinical Genetics
- Vol. 20 (4), 304-309
- https://doi.org/10.1111/j.1399-0004.1981.tb01037.x
Abstract
In 100 children with Down syndrome (DS), the parental origin of the supernumery chromosome 21 was investigated. In 76 out of the 100 cases the polymorphic regions were informative, i.e. 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 less than 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 less than 0.001) of non-M PI variants was found in their mothers, particularly when only the MS and MZ types which are recognised as deficiency variants were considered. Most striking, however, is the almost 5-fold increased frequency of MS and MZ types found in mothers where the nondisjunction had occurred during the first meiotic division. This would suggest that PI deficiency interferes with some process leading to non-disjunction. If these findings are confirmed, application of Bayes' theorem enables us to estimate 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 counselling and enhance the benefits of prenatal diagnosis programmes.Keywords
This publication has 15 references indexed in Scilit:
- Alpha-1-antitrypsin (Pi) types in Down's syndromeClinical Genetics, 2008
- Antiproteases and Down's syndrome in an Australian population.Journal of Medical Genetics, 1980
- Some Aspects on the Organization of Microfilaments and Microtubules in Relation to NondisjunctionEnvironmental Health Perspectives, 1979
- α1‐Antitrypsin deficiency in twins and parents‐of‐twinsClinical Genetics, 1979
- Separator isoelectric focusing for identification of α-1-antitrypsin (Pi M) subtypesScandinavian Journal of Clinical and Laboratory Investigation, 1978
- Alpha‐1‐antitrypsin (Pi)‐types in recurrent miscarriagesClinical Genetics, 1978
- The origin of the extra chromosome 21 in Down syndromeCytogenetic and Genome Research, 1978
- Increased frequency of heterozygotes for α1 antitrypsin variants in individuals with either sex chromosome mosaicism or trisomy 21Nature, 1976
- Alpha1-antitrypsin phenotypes in sex chromosome mosaicism.Journal of Medical Genetics, 1975
- Ribosomal DNA Connectives between Human Acrocentric ChromosomesNature, 1973