Novel nucleotide insertions in two unrelated Indian patients with 5 alpha reductase 2 deficiency leading to premature termination of SRD5A2 enzyme

作者：Shabir Iram; Khurana Madan L; Marumudi Eunice; Khadgawat Rajesh; Ammini Ariachery C^*

来源：Steroids, 2013, 78(12-13): 1159-1163.

DOI：10.1016/j.steroids.2013.08.010

• SRD5A2 gene
• Dihydrotestosterone
• 46, XY DSD
• c.188_189insTA

T is converted to a more potent androgen, DHT by the action of microsomal membrane enzyme 5 alpha reductase 2. Defects in 5 alpha 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 5 alpha RD2 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 5aRD2 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.

• 出版日期2013-12-11
• 单位河北医科大学