Simultaneous novel mutations in the BCORL1 and AUTS2 genes detected by next-generation sequencing in a Vietnamese male patient with intellectual disability

  • Đào Phương Giang Bệnh viện Trung ương Quân đội 108
  • Đinh Thị Thảo Bệnh viện Trung ương Quân đội 108
  • Trần Ngọc Khánh Duyên Bệnh viện Trung ương Quân đội 108
  • Bạch Thùy Dương Bệnh viện Trung ương Quân đội 108
  • Nghiêm Xuân Hoàn Bệnh viện Trung ương Quân đội 108

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Keywords

BCORL1, AUTS2, Intellectual disability, pathogenic variant.

Abstract

Intellectual disability can be caused by various genetic etiologies, among which novel mutations in the BCORL1 and AUTS2 genes have been individually reported to be associated with intellectual disability and neurodevelopmental disorders. We report the first Vietnamese male patient carrying concurrent novel mutations in both the BCORL1 and AUTS2 genes detected by next-generation sequencing, aiming to emphasize the value of genetic diagnostic analysis in complex cases. Case presentation: The patient is a 16-year-old male of Kinh ethnicity, who experienced psychomotor and language delay since early childhood, currently presenting with mild-to-moderate intellectual disability accompanied by mild autism spectrum disorder (ASD). The patient underwent G-banded karyotyping and next-generation sequencing using a panel of 4,503 genes related to neurodevelopmental disorders. Variants were classified according to ACMG/AMP 2015 criteria and confirmed by Sanger sequencing in the patient and family members. Discussion: The patient exhibited facial features suggestive of AUTS2 syndrome, with no organ malformations or epilepsy. Karyotype and CNV analysis were normal. The NGS panel of 4,503 genes identified two rare variants: (i) A novel missense variant in BCORL1  in a hemizygous state in exon 4, located within the hotspot region causing Shukla-Vernon syndrome; (ii) A novel frameshift variant in AUTS2  in a heterozygous state in exon 8, predicted to cause loss of function of the long allele via nonsense-mediated decay. Both variants were absent from gnomAD/ClinVar/HGMD, were predicted to be deleterious by multiple in silico prediction algorithms, and were classified as "likely pathogenic" according to ACMG criteria. Sanger sequencing confirmed that the BCORL1 variant was inherited from the heterozygous mother following an X-linked recessive pattern, while the AUTS2 variant was de novo. Conclusion: This is the first case in Vietnam documenting the combination of novel variants in BCORL1 and AUTS2 in a male patient with intellectual disability, highlighting the importance of genetic counseling and long-term multidisciplinary management.

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References

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Published
Apr 24, 2026
DOI: https://doi.org/10.52389/ydls.v21i3.3000
Issue
Volume 21 - No 3/2026
Section
Articles
How to Cite
Giang Đào P., Thảo Đinh T., Khánh DuyênT. N., DươngB. T., & HoànN. X. (2026). Simultaneous novel mutations in the BCORL1 and AUTS2 genes detected by next-generation sequencing in a Vietnamese male patient with intellectual disability. Tạp Chí Y Dược lâm sàng 108, 21(3). https://doi.org/10.52389/ydls.v21i3.3000