Defining p47-phox deficient Chronic Granulomatous Disease in a Malay family

Background: The most common autosomal form of Chronic Granulomatous Disease, p47-phox deficient CGD, generally features a GT (Delta GT) deletion in the GTGT sequence at the start of exon 2 on the NCF-1 gene. This consistency is due to the coexistence of and the recombination between 2 homologous pseudogenes (psi s) and NCF-1. The GTGT: AGT ratio mirrors the NCF-1: NCF-1 psi ratio and is 2:4 in normal individuals. Objective: To determine the molecular basis of the Autosomal-CGD in a family with 2 children, a male and female, affected by the disease. The female patient suffered recurrent infection, retinitis pigmentosa and discoid lupus. Methods: Chemiluminescence (CL) was used to study the respiratory burst, while genetic analysis was done by RT-PCR, PCR, AGT and the 20bp gene scans. Results: The CL response of the patient was profoundly low. The patient's. p47-phox band was absent in the RT-PCR for NADPH-oxidase component mRNAs. The Delta GT scan showed that the patient's GTGT: Delta GT ratio was 0:6, the parents' and the younger brother's was 1:5 and the younger sister's was 2:4. Examination of other NCF-1/ NCF-1 psi s differences showed that the father had a compound Delta GT allele ie. Delta GT-20bp, inherited by the patient, and that both parents had compound GTGT alleles with a single 30bp segment in intron 1. Conclusions: The patient was a classic, homozygous Delta GT p47-phox deficient CGD with one allele harbouring a compound Delta GT-20bp gene. The Delta GT and 20bp gene scans offer a relatively simple and efficient means of defining a p47-phox deficient CGD patient.