Intellectual disability in two Chinese sisters caused by a 3p26.3p25.3 microdeletion and a 14q32.13q32.33 microduplication inherited from the mother with 46, XX, t (3, 14) (p25; q32).

Background: Genetic factors associated with intellectual disability (ID) include chromosomal aberrations, copy number variations (CNVs), and pathogenic variants. Identifying the genetic etiologies is beneficial for patient classification, therapy, management, and prognostic evaluation. Emerging genetic tests are helpful in identifying these genetic causes.

Methods: We enrolled two girl siblings with ID. Trio whole-exome sequencing (WES) and Copy number variation sequencing (CNV-Seq) were performed for genetic molecular analysis in these probands and their parents. The parents also accepted high-resolution G-banded karyotype studies.

Results: No significant homozygous or heterozygous variants were identified through WES. By CNV-seq, we identified an abnormal 3p26.3p25.3 microdeletion and 14q32.13q32.33 microduplication in the two girl siblings but not in their parents. A balanced translocation 46, XX, t (3, 14) (p25; q32) was found in their mother.

Conclusion: The affected siblings have similar phenotype, including ID, short stature, and microcephaly. Their mother had a history of seven first-trimester miscarriages and one elective termination because of multiple malformations. This abnormal karyotype was also thought to be responsible for the mother's recurrent miscarriage. WES in combination with CNV-seq analysis is very helpful for identification of the genetic causes of ID without positive karyotype findings.