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

• DOI: 10.3389/fgene.2023.1290949
• Publication Date: 2023-12-20T07:54:52Z
• Authors: Cheng Huang; Haiyan Luo; Baitao Zeng; Chuanxin Feng; Jia Chen; Huizhen Yuan; Shuhui Huang; Bicheng Yang; Yongyi Zou; Yanqiu Liu
• Keywords: Proband; Microcephaly; Sanger sequencing

Background and purpose: Intellectual disability-7 (MRD7) is a subtype disorder of intellectual disability (MRD) involving feeding difficulties, hypoactivity, febrile seizures at an age early onset, then progressive physical development deterioration. We purposed to identify the underlying causative genetic factors three individuals in each Chinese family who presented with symptoms facial dysmorphic features. provided prenatal diagnosis for families counseling prevention this disease. Methods: collected retrospective clinical diagnostic evidence probands our study, which included magnetic resonance imaging (MRI), computerized tomography (CT), electroencephalogram (EEG), intelligence tests study. Genetic investigation their next kin was performed by Trio-whole exome sequencing (WES). Sanger or quantitative PCR technologies were used as step verify variants confirmed Trio-WES families. Moreover, we amniocentesis explore state pathogenic fetuses molecular appropriate gestational period Results: The one fetus clinically diagnosed microcephaly exhibited developmental disability, postnatal Combining probands’ manifestations, uncovered heterozygous DYRK1A : novel variant exon3_exon4del p.(Gly4_Asn109del), c.1159C>T p.(Gln387*), previously but rare c.1309C>T p.(Arg437*) (NM_001396.5) families, respectively. In light updated American College Medical Genomics (ACMG) criterion, both classified likely (PSV1+PM6), while c1309C>T identified (PVS1+PS2_Moderate+PM2). Considering features testimony, MRD7. These discovered considered causal mutations Prenatal detected dominant p.(Gln387*) fetuses, indicating significant probability MRD7, subsequently gestation intervened parents’ determination professional obstetrical operation. On other side, testing revealed wild-type alleles two parents decided sustain gestation. Conclusion: mutation has broadened spectrum MRD7 level. Besides, study supported determine efficiently provide concise using technology.