Patients 1–3, 6, and 7 were studied using whole-exome/genome (WES/WGS) sequencing. For patient 1, WES was performed on a SOLiD 5500XL sequencing platform (Life Technologies, Foster City, CA). Short reads were mapped against the GRCh37/hg19 human assembly by means of LifeScope software (Life Technologies). Variants were detected using the Haplotype Caller software package of the Genome Analysis Toolkit (GATK) suite and filtered to include only variants covered by at least 10 reads with mapping quality values exceeding 30. For patients 2, 3, and 6, WGS was performed with Illumina TruSeq DNA PCR-Free Sample Preparation kit on an Illumina Hiseq 2500 sequencing platform (Illumina Inc., San Diego, CA). For patient 3, WGS was performed as part of the National Institute for Health Research Bioresource Rare Disease Project. A minimum coverage of 15X (95% of the genome) was obtained, with an average coverage of ∼30X. Reads were aligned using Isaac aligner (version 01.14) (Illumina Inc., Great Chesterford, UK) and mapped against the GRCh37 hg19 human assembly. Single nucleotide variants and insertions/deletions were identified using Isaac variant caller. Patients 4 and 5 were
