Background: Mutations in the X-chromosomal androgen receptor (AR) gene, rendering the AR protein completely or partially inactive, cause complete or partial (PAIS) androgen insensitivity syndrome.
Case report: The proband was born at term following uneventful pregnancy. His phallus length was 28 mm, he had palpable gonads in the lower portion of the inguinal canal, and he had a severe penoscrotal hypospadia. His karyotype was 46,XY, and molecular karyotype (defined by array comparative genomic hybridization) was normal. At 7 days of age, his serum testosterone was 0.7 nM and increased to 20 nM in human chorionic gonadotropin stimulation test. Sequencing of the AR gene revealed a 148 bp deletion in exon 1. This mutation, c.108_255del (p.Pro37Serfs*89), leads to premature stop codon truncating over 90% of the 920 amino acid receptor. However, the PCR amplification and sequencing of the genomic DNA from the probands peripheral blood leukocytes showed also the existence of the normal allele without the deletion, implying somatic mosaicism and de novo origin of the mutation. His mother only displayed one PCR band consistent with normal AR.
Conclusions: Mutations in AR that completely inactivate the receptor may manifest as PAIS due to somatic mosaicism.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology