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Purpose <p>Complete Androgen Insensitivity Syndrome (CAIS) is a rare X-linked disorder caused by pathogenic variants in the androgen receptor (<i>AR</i>) gene, leading to resistance to androgens in individuals with a 46, XY karyotype.</p> Materials and methods <p>This study aims to describe the clinical and genetic profile of CAIS patients from a tertiary care hospital in northern India. Thirteen consecutive patients with a clinical diagnosis of CAIS evaluated at our centre between August 2013 to May 2025 were included. The evaluation included detailed clinical assessment, hormonal evaluation and genetic analysis. Genetic analysis was performed by using a customized next-generation sequencing panel that included <i>AR</i> gene and nine other genes including <i>WNT4</i>,<i> SRD5A2</i>,<i> CYP21A2</i>,<i> POR</i>,<i> HSD17B3</i>,<i> NR5A1</i>,<i> CYP17A1</i>,<i> SOX9</i>, and <i>CYP11B1</i>. The panel covered whole genes including non-coding regions (splice-site and introns).</p> Results <p>Ten patients presented at puberty with primary amenorrhea and three patients presented in the pre-pubertal period with bilateral inguinal hernias and phenotypically female external genitalia. Pathogenic or likely pathogenic <i>AR</i> variants were identified in 10 of 13 (76.9%) patients. These include likely three novel variants (missense variant c.2198&#xa0;A &gt; G; in-frame long deletion c.403_1420delGCGG and splice-site deletion c.1616+3_1616 + 6delAAGT) and two known variants (frameshift insertion c.239_240insGCAGCAGC and canonical splice-site variant c. 2608-1G &gt; T). Notably, 7 of the 10 variants were splice-site variants.</p> Conclusion <p>This is the largest study of CAIS patients from India. The main contribution of our study is the detection of likely three novel and two known pathogenic variants of <i>AR</i> gene associated with CAIS in a Kashmiri cohort. The high frequency of splice-site variants highlights the need to include non-coding regions in the analysis of <i>AR</i> gene for accurate molecular diagnosis.</p>

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Clinical and genetic characteristics of patients with complete androgen insensitivity syndrome: an experience from a tertiary care centre of Kashmir Valley

  • 期刊论文

  • 发表日期：

    2026年8月3日

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  • Raiz Ahmad Misgar,
  • Sajad Ul Isam Mir,
  • Shariq Rashid Masoodi,
  • Ajaz Qadir,
  • Imtiyaz Ahmad Bhat,
  • Zafar Amin Shah,
  • Mir Iftikhar Bashir,
  • Arshad Iqbal Wani

摘要

Purpose

Complete Androgen Insensitivity Syndrome (CAIS) is a rare X-linked disorder caused by pathogenic variants in the androgen receptor (AR) gene, leading to resistance to androgens in individuals with a 46, XY karyotype.

Materials and methods

This study aims to describe the clinical and genetic profile of CAIS patients from a tertiary care hospital in northern India. Thirteen consecutive patients with a clinical diagnosis of CAIS evaluated at our centre between August 2013 to May 2025 were included. The evaluation included detailed clinical assessment, hormonal evaluation and genetic analysis. Genetic analysis was performed by using a customized next-generation sequencing panel that included AR gene and nine other genes including WNT4, SRD5A2, CYP21A2, POR, HSD17B3, NR5A1, CYP17A1, SOX9, and CYP11B1. The panel covered whole genes including non-coding regions (splice-site and introns).

Results

Ten patients presented at puberty with primary amenorrhea and three patients presented in the pre-pubertal period with bilateral inguinal hernias and phenotypically female external genitalia. Pathogenic or likely pathogenic AR variants were identified in 10 of 13 (76.9%) patients. These include likely three novel variants (missense variant c.2198 A > G; in-frame long deletion c.403_1420delGCGG and splice-site deletion c.1616+3_1616 + 6delAAGT) and two known variants (frameshift insertion c.239_240insGCAGCAGC and canonical splice-site variant c. 2608-1G > T). Notably, 7 of the 10 variants were splice-site variants.

Conclusion

This is the largest study of CAIS patients from India. The main contribution of our study is the detection of likely three novel and two known pathogenic variants of AR gene associated with CAIS in a Kashmiri cohort. The high frequency of splice-site variants highlights the need to include non-coding regions in the analysis of AR gene for accurate molecular diagnosis.