Abstract
Intellectual disability (ID) is still unexplained in 60% of cases and prenatal diagnosis is very challenging for this condition. A second gravida presented to us at 6 weeks of gestation for counseling. Her previous child had been diagnosed with ID and autism. Detailed family history showed that her brother also had ID. Screening investigations were normal for the affected child. Exome sequencing report revealed variation of unknown significance (VOUS) on SIN3A gene and UPF3B gene. The variation in X-linked UPF3B gene was reclassified as novel pathogenic variation after segregation studies with parents and affected maternal uncle for both the genes variations. An amniocentesis was done at 18 weeks gestation for the novel mutation in the UPF3B gene and the fetus was found unaffected. The patient delivered a healthy male child who is doing well at two years of age. To conclude, we should not disregard VOUS on exome sequencing. Identification of VOUS requires careful genotype-phenotype correlation and segregation studies to counsel parents regarding the risk of having another affected child.
Keywords
Intellectual disability - X-linked - Autism -
UPF3B gene - Variation
