A novel breakpoint deletion within a CAG repeat causes complete androgen insensitivity syndrome: Report of its segregation in a large Czech family.
TL;DR
A unique AR deletion identified in a 46,XY female patient with CAIS is described, which segregates in the large CAIS family; it was detected in five affected relatives, while the four remaining family members were asymptomatic carriers.
Abstract
Background
Complete androgen insensitivity syndrome (CAIS) is one of the most prevalent conditions of disorders/differences of sex development (DSD), with an X-linked recessive inheritance. A hemizygous pathogenic variant in the AR gene causes the condition. CASE REPORT We present a five-generation Czech family with several CAIS-positive relatives. The proband is a 27-year-old female patient with a 46,XY karyotype, who exhibits the typical CAIS phenotype. This includes female external genitalia, the absence of uterus, a blind-ending vagina, undescended testes, and almost missing axillary and pubic hair.
Methods
AND
Results
We identified a novel pathogenic, hemizygous NM_000044.4(AR):c.-66_220del p.? variant using Sanger DNA sequencing with specifically designed primers. This AR deletion was 286 bp in length and initiated in the 5'-UTR, terminating within the polymorphic CAG repeats in exon 1 of the AR gene. The AR variant removed the original initiation codon ATG, resulting in a shortened AR transcript with an unknown effect on the translation.
Conclusion
We describe a unique AR deletion identified in a 46,XY female patient with CAIS. The variant segregates in the large CAIS family; it was detected in five affected relatives, while the four remaining family members were asymptomatic carriers.