AIMTo identify the genotype of two Indians with male pseudohermaphroditism.

METHODSStandard radioimmunoassay procedure was used for estimating hormonal levels. Conventional cytogenetic analysis was carried out for diagnosing the genetic sex in these subjects with genital ambiguity. Molecular analysis was carried out by standard polymerase chain reaction procedure using different sets of primers and reaction conditions specific for the 5alpha-reductase type 2 gene (SRD5A2) gene. Direct sequencing was carried out using the ABI Prism dye terminator sequencing kit and the ABI 310 sequencing apparatus.

RESULTSWe found an SRD5A2 gene mutation in exon 5, where arginine is substituted with glutamine (R246Q), in two males with pseudohermaphroditism and ambiguous genitalia from unrelated families. This is the first time this mutation has been reported in individuals from India.

CONCLUSIONIdentification of the R246Q mutation of the SRD5A2 gene from two unrelated Indian families possibly extends the founder gene effect.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase ; genetics ; Child ; Dihydrotestosterone ; blood ; Disorders of Sex Development ; genetics ; pathology ; Family Health ; Follicle Stimulating Hormone ; blood ; Founder Effect ; Genitalia, Male ; abnormalities ; Humans ; Hypospadias ; genetics ; pathology ; India ; Luteinizing Hormone ; blood ; Male ; Mutation, Missense ; Testosterone ; blood

Phagocytes such as neutrophils play a vital role in host defense against microbial pathogens. The anti-microbial function of neutrophils is based on the production of superoxide anion (O2(.-)), which generates other microbicidal reactive oxygen species (ROS) and release of antimicrobial peptides and proteins. The enzyme responsible for O2(.-) production is called the NADPH oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two transmembrane proteins (p22phox and gp91phox, also called NOX2, which together form the cytochrome b(558)) and four cytosolic proteins (p47phox, p67phox, p40phox and a GTPase Rac1 or Rac2), which assemble at membrane sites upon cell activation. NADPH oxidase activation in phagocytes can be induced by a large number of soluble and particulate agents. This process is dependent on the phosphorylation of the cytosolic protein p47phox. p47phox is a 390 amino acids protein with several functional domains: one phox homology (PX) domain, two src homology 3 (SH3) domains, an auto-inhibitory region (AIR), a proline rich domain (PRR) and has several phosphorylated sites located between Ser303 and Ser379. In this review, we will describe the structure of p47phox, its phosphorylation and discuss how these events regulate NADPH oxidase activation.
*Disease ; Enzyme Activation ; Humans ; Membrane Glycoproteins/chemistry/*metabolism ; NADPH Oxidase/chemistry/genetics/*metabolism ; Phagocytes/cytology/*metabolism ; Phosphorylation ; Protein Conformation