Genetic and Biochemical Consequences of Adenosine Deaminase Deficiency in Humans

345-356Adenosine deaminase deficiency accounts for ~15-20% of severe combined immunodeficiency in humans. The gene for adenosine deaminase is located on chromosome 20q12-q13.11 and codes for an aminohydrolase that catalyzes the deamination of adenosine and deoxyadenosine to inosine and deoxyinosine, respectively. Absence of the enzyme causes a build-up of the substrates in addition to excess deoxyadenosine triphosphate, thereby compromising the regenerative capacity of the immune system. Due to underlying allelic heterogeneity, the disorder manifests as a spectrum, ranging from neonatal onset severe combined immunodeficiency to apparently normal partial adenosine deaminase deficiency. Tandem mass spectrometry coupled with high efficiency separation systems enables postnatal diagnosis of the disorder, while prenatal diagnosis relies on assaying enzyme activity in cultured amniotic fibroblasts or chorionic villi sampling. Screening of adenosine deaminase deficiency for relatives-at-risk may reduce costs of treatment and ensure timely medical intervention as applicable. This article reviews the genetic, biochemical and clinical aspects of adenosine deaminase deficiency

Discerning non-disjunction in down syndrome patients by means of GluK1-(AGAT) n and D21S2055-(GATA) n microsatellites on chromosome 21

Introduction: Down syndrome (DS), the leading genetic cause of mental retardation, stems from non-disjunction of chromosome 21. Aim: Our aim was to discern non-disjunction in DS patients by genotyping GluK1-(AGAT) n and D21S2055-(GATA) n microsatellites on chromosome 21 using a family-based study design. Materials and Methods: We have used a PCR and automated DNA sequencing followed by appropriate statistical analysis of genotype data for the present study Results and Discussion: We show that a high power of discrimination and a low probability of matching indicate that both markers may be used to distinguish between two unrelated individuals. That the D21S2055-(GATA) n allele distribution is evenly balanced, is indicated by a high power of exclusion [PE=0.280]. The estimated values of observed heterozygosity and polymorphism information content reveal that relative to GluK1-(AGAT) n [H obs =0.286], the D21S2055- (GATA) n [H obs =0.791] marker, is more informative. Though allele frequencies for both polymorphisms do not conform to Hardy-Weinberg equilibrium proportions, we were able to discern the parental origin of non-disjunction and also garnered evidence for triallelic (1:1:1) inheritance. The estimated proportion of meiosis-I to meiosis-II errors is 2:1 in maternal and 4:1 in paternal cases for GluK1-(AGAT) n , whereas for D21S2055-(GATA) n , the ratio is 2:1 in both maternal and paternal cases. Results underscore a need to systematically evaluate additional chromosome 21-specific markers in the context of non-disjunction DS