Copy number variant analysis by exome sequencing is an effective approach to optimize diagnostic yield for developmental disorders-the DDD-Africa study.

CNV detection integrated into exome analysis using CANOES and XHMM, with inheritance assessment from parental data

This study developed an approach to integrate CNV detection directly into the exome analysis pipeline of the DDD-Africa cohort, at no additional laboratory cost. Exome data from 505 probands with a developmental disorder were analyzed using CANOES and XHMM, with parental DNA used to assess inheritance patterns when available. A diagnosis was confirmed in 41/505 patients (8.1%), with 43 pathogenic CNVs identified (31 deletions, 12 duplications). Among the 26 probands with parental data, all identified CNVs were de novo. Adding CNV analysis increased diagnostic yield by 8.1%, an approach well suited to low- and middle-income countries.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A high-impact practical work: extracting CNVs from the same exome dataset avoids a complementary microarray and boosts yield at no extra cost, a decisive argument for resource-limited laboratories. The approach relies on established tools (CANOES, XHMM) validated on real patient data. The 8.1% gain is consistent with the literature and reinforces exome as a single test capable of capturing both SNVs and CNVs.

Analysis by Dr Thibaut Benquey