Prenatal diagnosis of JAK3 deficient SCID.
The JAK3 gene, encoding a tyrosine kinase functionally coupled to cytokine receptors which share the common gamma chain, has been identified as the defective gene for autosomal recessive severe combined immunodeficiency (SCID). Thus, specific mutational diagnosis has become possible. We screened all exons with a combined single strand conformational polymorphism and hetero-duplex formation assay followed by sequence analysis to identify specific mutations in two families. This assay was used on chorionic villus sampling derived DNA in two fetuses from two unrelated families, where we found mutations in both parents. We were able to exclude the mutations in both fetuses by the 12th week of gestation. The described method for first-trimester prenatal diagnosis of autosomal recessive T-B+SCID provides a valid tool to aid in genetic counselling and possibly prenatal therapy in this disease.
Department of Paediatrics, University of Brescia, Brescia, Italy. schumach@master.cci.unibs.it
R F
RF
Schumacher
P
P
Mella
F
F
Lalatta
M
M
Fiorini
S
S
Giliani
A
A
Villa
F
F
Candotti
L D
LD
Notarangelo
D000483:Alleles; D015193:Chorionic Villi Sampling; D004247:DNA / Q000032:analysis; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D053616:Janus Kinase 3; D018655:Lymphocyte Count; D008297:Male; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics*; D017422:Sequence Analysis, DNA; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics
D004247:DNA; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3