The phenotype of each patient was evaluated by a clinical geneticist in each collaborating center. Patients 1 to 3, 17, and 20 to 22 were diagnosed by singleton ES with familial segregation analysis by Sanger sequencing, except for patient 17 for whom parental samples were unavailable. Patients 4 to 14, 16, 18, and 19 were diagnosed using trio ES. Next-generation sequencing was performed at each local center, using the following platforms: HiSeq for patients 1 to 3, 5 to 9, 12, 17, 20, and 21 ;
NextSeq for patients 13 and 14; and
NovaSeq for patients 11, 15, (
link)17 to 19, and 22 (Illumina) . SOLiD system sequencing (Life Technologies) was used for patient 10. The deletions of patients 15 and 22 were discovered by single-nucleotide variant (formerly single-nucleotide polymorphisms)-array analysis using a
CytoSNP-850K BeadChip (Illumina). Details of the sequencing method, kits, and tools used by each center are described in the Supplemental material and method. Variant interpretation and classification was done adhering to American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines. All single-nucleotide variants and indel nomenclature were verified in VariantValidator and submitted in ClinVar (see Web Resources) with the following accession numbers: SCV002016268.1, SCV002016269.1, then SCV002055998 to SCV002056014.
Cuinat S., Nizon M., Isidor B., Stegmann A., van Jaarsveld R.H., van Gassen K.L., van der Smagt J.J., Volker-Touw C.M.L., Holwerda S.J.B., Terhal P.A., Schuhmann S., Vasileiou G., Khalifa M., Nugud A.A., Yasaei H., Ousager L.B., Brasch-Andersen C., Deb W., Besnard T., Simon M.E.H., Amsterdam K.H., Verbeek N.E., Matalon D., Dykzeul N., White S., Spiteri E., Devriendt K., Boogaerts A., Willemsen M., Brunner H.G., Sinnema M., De Vries B.B.A., Gerkes E.H., Pfundt R., Izumi K., Krantz I.D., Xu Z.L., Murrell J.R., Valenzuela I., Cusco I., Rovira-Moreno E., Yang Y., Bizaoui V., Patat O., Faivre L., Tran-Mau-Them F., Vitobello A., Denommé-Pichon A.S., Philippe C., Bezieau S, & Cogné B. (2022). Loss-of-function variants in SRRM2 cause a neurodevelopmental disorder. Genetics in medicine : official journal of the American College of Medical Genetics, 24(8).
