Identification of two novel and one rare mutation in DYRK1A and Prenatal diagnoses in three Chinese families with Intellectual Disability-7

The three probands and one fetus were clinically diagnosed with microcephaly and exhibited intellectual developmental disability, postnatal feeding difficulties and facial dysmorphic features. Combining probands’clinical manifestations, Trio-WES uncovered the three heterozygous variants in DYRK1A: a novel variant exon3_exon4del p.(Gly4_Asn109del), a novel variant c.1159C>T p.(Gln387*) and a previously presented but rare pathogenic variant c.1309C>T p. (Arg437*) (NM_001396.5) in three families, respectively. In light of the updated American college of Medical Genetic and Genomics (ACMG) criterion, the variant of exon3_exon4del and c.1159C>T were both classified as likely pathogenic (PSV1+PM6), while c1309C>T was identified as pathogenic (PVS1+PS2_Moderate+PM2). Considering with clinical features and molecular testimony, the three probands were confirmly diagnosed with MRD7. These three discovered variants were considered as the three families'causal mutations for MRD7. Prenatal diagnosis detected the heterozygous dominant variant of c.1159C>T p.(Gln387*) in one of the fetuses, indicating a significant probability of MRD7, subsequently the gestation was intervened by the parents’determination and professional obstetrical operation. On the other side, prenatal molecular genetic testing revealed wild type alleles in the other two fetuses and their parents both decided tosustain the gestation.