The diagnostic yield of intellectual disability: combined whole genome low-coverage sequencing and medical exome sequencing

Abstract

Background: Intellectual disability (ID) is a heterogeneous neurodevelopmental disorder with a complex genetic underpinning in its etiology. Chromosome microarray (CMA) is recommended as the first-tier diagnostic test for ID due to high detection rate of copy number variation (CNV). Methods: To identify an appropriate clinical detection scheme for ID in Han Chinese patients, whole genome lowcoverage sequencing was performed as the first-tier diagnostic test, and medical exome sequencing (MES) as the second-tier diagnostic test for patients with negative results of CNVs. Results: A total of 19 pathogenic CNVs in 16/95(16.84%) ID patients and 10 pathogenic single-nucleotide variations (SNVs), including 6 novel mutations in 8/95(8.42%) ID patients were identified on whom no pathogenic CNVs were discovered. The detection rate of CNVs in ID with multiple congenital anomalies (MCA) subgroup was significantly higher than ID with autism spectrum disorders and other IDs subgroups. And the single-nucleotide variations showed a higher occurrence rate in the other IDs subgroup. Conclusions: There were differences in the diagnostic yields of different variation types among the three ID subgroups. Our findings provided a new perspective on appropriate clinical detection scheme in different ID subgroups based on statistically significant differences among the three ID subgroups. The application of whole genome low-coverage sequencing as the first-tier diagnostic test for ID with MCA subgroup and MES as the firsttier diagnostic test for other ID subgroup was considered as an efficient clinical detection scheme.

Information is power: The experiences, attitudes and needs of individuals who chose to have prenatal genomic sequencing for fetal anomalies

“…It is one of the most effective genetic diagnostic methods, and medical and personal utility has been repeatedly demonstrated. [1][2][3][4] Studies have demonstrated the potential utility of prenatal genomic sequencing (pGS) with diagnostic yields from 5% to 57% depending on prenatal phenotype. [5][6][7][8][9][10][11][12] A prenatal genetic diagnosis has valuable medical utility: prenatally, it can guide fetal intervention and delivery plans and postnatally, it can help target treatment, avoid unnecessary evaluations and ensure early initiation of therapies, sometimes before symptoms occur.…”

Genetic and phenotypic analysis of 225 Chinese children with developmental delay and/or intellectual disability using whole-exome sequencing

“…WES was performed and analyzed by (Kaiumph Medical Diagnostic Lo. Ltd, (Beijing, China) [ 19 ], Angen Gene Medicine Tech (Beijing, China) [ 20 ] or Running Gene Inc. (Beijing, China) [ 21 ] using their own bioinformatics pipelines as previously described. The laboratory-specific WES methodologic parameters were shown in Supplementary Table 1.…”

Ehlers-Danlos Syndrome in the Field of Psychiatry: A Review

“…Neurodevelopment disorders (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) Anorexia nervosa (12,(23)(24)(25)(26)(27)(28)(29)(30) Addiction (33,34) Anxiety disorders (35)(36)(37)(38)(39)(40)(41)(42)(43) Mood disorders (17,37,(45)(46)(47)(48)(49)(50) Personality disorder (42,49,64)…”

“…Wang et al performed whole-genome low-coverage sequencing and medical exome sequencing and found a case with B4GALT7 gene variants associated with spondylodysplastic-type spEDS. The common symptoms of this type of EDS include progressive short stature from childhood, hypotonia, and bowing of limbs, and some minor symptoms include skin hyperextensibility, pes planus, delayed motor development, and mild intellectual disabilities ( 11 ). One of the patients we reported on ( 12 ) had moderate intellectual disabilities and did not have some of the clinical symptoms, such as short stature and sparse scalp hair and eyebrows.…”