title: Novel nucleotide insertions in two unrelated Indian patients with 5α reductase 2 deficiency leading to premature termination of SRD5A2 enzyme.
abstract: T is converted to a more potent androgen, DHT by the action of microsomal membrane enzyme 5α reductase 2. Defects in 5α reductase 2 isozyme results in incomplete virilisation of external male genitalia. Mutations in SRD5A2 gene leads to diminished enzyme activity, thus hampering DHT synthesis from T. We describe two unrelated patients from India with 5αRD2 due to novel insertion of nucleotides in the exon 1 of SRD5A2 gene that lead to premature termination of protein. Master S (case 1; III.8) was 3 years old at initial evaluation, had perineoscrotal hypospadias, microphallus and both testes were palpable in the inguinal region. Master P (case 2; III.9) was born as normal full term baby. He had primary complaint of microphallus, penoscrotal hypospadias and gonads in the inguinal region. Diagnosis of 5αRD2 was made, as T/DHT ratio in the two cases was 41 and 131.2 respectively. Sequence analysis of SRD5A2 gene showed an insertion of nucleotides TA in exon 1 (c.188_189). This resulted in premature termination of the protein due to stop codon at amino acid position 7. The protein formed is drastically truncated and inadequate protein synthesized explains the phenotypic characteristics of our patients.
authors.affiliation: Department of Endocrinology & Metabolism, All India Institute of Medical Sciences, New Delhi 29, India.
authors.forename: Iram
authors.initials: I
authors.lastname: Shabir
authors.forename: Madan L
authors.initials: ML
authors.lastname: Khurana
authors.forename: Eunice
authors.initials: E
authors.lastname: Marumudi
authors.forename: Rajesh
authors.initials: R
authors.lastname: Khadgawat
authors.forename: Ariachery C
authors.initials: AC
authors.lastname: Ammini
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D056726:Genetic Association Studies; D005832:Genital Diseases, Male / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D007194:India; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010375:Pedigree; D010413:Penis / Q000002:abnormalities* / Q000201:enzymology
chemical_list: D018389:Codon, Nonsense; D008565:Membrane Proteins; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548468:SRD5A2 protein, human
keywords: 46, XY DSD; Dihydrotestosterone; SRD5A2 gene; c.188_189insTA