Identification and prenatal diagnosis of a novel likely pathogenic ANOS1 variant in a large Chinese Kallmann syndrome family.

A novel ANOS1 c.1879T>C variant was identified as likely pathogenic in a large Chinese Kallmann syndrome family, fully co-segregating with the disease in tested members.

• Why it matters: Understanding genetic causes of Kallmann syndrome is essential for accurate diagnosis and genetic counseling, especially when functional studies are lacking.
• What they did: Researchers performed whole-genome and Sanger sequencing on 40 family members, used bioinformatics and AlphaFold3 modeling to assess the variant’s impact, and conducted prenatal diagnosis for a female carrier.
• The result: The variant was classified as likely pathogenic, enabling precise genetic counseling and prenatal testing, demonstrating the value of family co-segregation analysis in variant interpretation without functional experiments.