An efficient genetic test flow for multiple congenital anomalies and intellectual disability

Abstract

Background: Genetic testing has enabled the diagnosis of multiple congenital anomalies and/or intellectual disabilities. However, because of the phenotypic variability in these disorders, selection of an appropriate genetic test can be difficult and complex. For clinical examination, particularly in clinical facilities, a simple and standardized system is needed. Methods: We compared microarray comparative genomic hybridization and clinical exome sequencing with regard to diagnostic yield, cost, and time required to reach a definitive diagnosis. After first performing G-banding for 200 patients with multiple congenital anomalies and/or intellectual disability, as a subsequent genetic test, microarray and clinical exome sequencing were compared with regard to diagnostic yield, cost, and time required.Results: There was no obvious difference in the diagnostic rate between the two methods; however, clinical exome sequencing was superior in terms of cost and time. In addition, clinical exome sequencing could sufficiently identify copy number variants, and even smaller copy number variants could be identified.Conclusions: Clinical exome sequencing should be implemented earlier as a genetic test for undiagnosed patients with multiple congenital anomalies and/or intellectual disabilities. Our results can be used to establish inspection methods in clinical facilities.

Decreased Microglia in Pax2 Mutant Mice Leads to Impaired Learning and Memory

“…A growing number of studies suggested that transcription factors play an important role in the process of neural development, and multiple genes encoding transcription factors had been identified as risk genes for neurodevelopmental disorders. , The transcription factor encoded by the Pax2 gene is expressed in the kidneys, eyes, ears, and CNS − and participates in the differentiation of early neural precursor cells. Mutations in Pax2 result in various diseases, such as renal dysplasia, abnormalities of the optic nerve, , and neurodevelopment disorders, including developmental delays, , epilepsy, , ID, , and ASD . In previous studies, we found that Pax2 +/– mice showed a high level of self-grooming behavior compared with wild-type mice .…”

“…24,25 The transcription factor encoded by the Pax2 gene is expressed in the kidneys, eyes, ears, and CNS 26−28 and participates in the differentiation of early neural precursor cells. Mutations in Pax2 result in various diseases, such as renal dysplasia, abnormalities of the optic nerve, 29,30 and neurodevelopment disorders, including developmental delays, 31,32 epilepsy, 33,34 ID, 35,36 and ASD. 36 In previous studies, we found that Pax2 +/− mice showed a high level of self-grooming behavior compared with wild-type mice.…”

Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease

“…The advent of technologies that allowed whole-genome analysis like CMA and NGS and its inclusion into medical practice has contributed to the identification of genetic causes related to CA. Association between pathogenic CNVs in patients presenting MCA and non-syndromic CA has been largely described [ 7 , 13 , 91 , 92 , 93 , 94 , 95 , 96 , 97 ], although only a few large cohort studies have been specifically performed aiming at analyzing the whole genome by array-CGH in samples with birth defects in Latin American populations [ 93 ]. Similarly, NGS data from patients with CA from our region is still scarcely represented in most of the clinical databases worldwide or in the literature [ 98 , 99 ].…”