Scholarlink

Purpose <p>Despite advances in genetic diagnostics, the molecular cause of a significant proportion of DSDs remains unknown. The aim of this study was to identify copy number variations (CNVs) using chromosomal microarray analysis (CMA) technology in DSD patients with previously undetected molecular genetic etiology and to investigate their phenotypic associations with these variations.</p> Methods <p>This study included DSD cases without chromosomal abnormalities and without any variants detected by sequence analysis methods, including whole-exome sequencing analysis. We evaluated variant pathogenicity according to the American College of Medical Genetics and Genomics guidelines and recorded the phenotypic findings of the cases. All pathogenic variants were subjected to segregation analysis.</p> Results <p>Of the 20 patients included in the study, 16 (80%) were classified as 46,XY DSD and 4 (20%) as 46,XX DSD. Initial clinical diagnoses in this 46,XX DSD group included gonadal dysgenesis in two patients (50%) and androgen excess in the remaining two (50%). Among the 46,XY DSD patients, five patients (31.25%) were presumed to be androgen insensitive, nine (56.25%) were diagnosed with defects in androgen biosynthesis, and two (12.5%) had gonadal dysgenesis. CMA detected 38 CNVs in 16 patients (80%), comprising 12 deletions (31.6%) and 26 duplications (68.4%). Three pathogenic CNVs were detected in 3 patients (15%), whereas 27 variants of uncertain significance were identified in 13 patients (65%).</p> Conclusion <p>In selected cases, the diagnostic approach should incorporate CMA to elucidate the molecular etiology of DSD. Furthermore, CMA may prove to be an invaluable tool in the search for new genes responsible for DSD.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Detection of copy number variations by chromosomal microarray analysis in disorders of sex development of unexplained molecular etiology and association with clinical findings

  • 期刊论文

  • 发表日期：

    2025年9月16日

查看全文
  • Murat Çağlar Karataş,
  • Ferda Evin,
  • Tahir Atik,
  • Aysun Ata,
  • Eren Er,
  • Erhan Parıltay,
  • Aslı Ece Solmaz,
  • Damla Gökşen,
  • Şükran Darcan,
  • Samim Özen

摘要

Purpose

Despite advances in genetic diagnostics, the molecular cause of a significant proportion of DSDs remains unknown. The aim of this study was to identify copy number variations (CNVs) using chromosomal microarray analysis (CMA) technology in DSD patients with previously undetected molecular genetic etiology and to investigate their phenotypic associations with these variations.

Methods

This study included DSD cases without chromosomal abnormalities and without any variants detected by sequence analysis methods, including whole-exome sequencing analysis. We evaluated variant pathogenicity according to the American College of Medical Genetics and Genomics guidelines and recorded the phenotypic findings of the cases. All pathogenic variants were subjected to segregation analysis.

Results

Of the 20 patients included in the study, 16 (80%) were classified as 46,XY DSD and 4 (20%) as 46,XX DSD. Initial clinical diagnoses in this 46,XX DSD group included gonadal dysgenesis in two patients (50%) and androgen excess in the remaining two (50%). Among the 46,XY DSD patients, five patients (31.25%) were presumed to be androgen insensitive, nine (56.25%) were diagnosed with defects in androgen biosynthesis, and two (12.5%) had gonadal dysgenesis. CMA detected 38 CNVs in 16 patients (80%), comprising 12 deletions (31.6%) and 26 duplications (68.4%). Three pathogenic CNVs were detected in 3 patients (15%), whereas 27 variants of uncertain significance were identified in 13 patients (65%).

Conclusion

In selected cases, the diagnostic approach should incorporate CMA to elucidate the molecular etiology of DSD. Furthermore, CMA may prove to be an invaluable tool in the search for new genes responsible for DSD.