Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. X:X | DOI: 10.5507/bp.2026.027

A novel breakpoint deletion within a CAG repeat causes complete androgen insensitivity syndrome: Report of its segregation in a large Czech family

Julia Martinkova1, Andrea Gregorova2, Marketa Wayhelova1, Jana Soukalova3, Miroslava Balascakova1, Anna Krepelova1
1 Department of Biology and Medical Genetics, Second Faculty of Medicine, Charles University in Prague and Motol and Homolka University Hospital, Prague, Czech Republic
2 Department of Medical Genetics, University Hospital Ostrava and University of Ostrava, Ostrava, Czech Republic
3 Department of Medical Genetics and Genomics, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic

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.

Keywords: disorders of sex development, androgen insensitivity syndrome, CAIS, AR gene

Received: March 2, 2026; Revised: July 7, 2026; Accepted: August 13, 2026; Prepublished online: August 25, 2026 

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