High-throughput SNP genotyping in families

High throughput SNP genotyping was carried out in all available family members of six different families (n = 34) (Fig. 1A) using the HumanOmniExpress Exome arrays v1.3 and the HiScanSQ system (Illumina Inc., San Diego, CA, USA). The GenomeStudio program (GS; Illumina) was used to undertake quality assessments and generate PLINK input reports for HM^{45 (link)}. Homozygous segments across all family members in each pedigree were determined as previously described, and only those shared by affected family members but not by healthy subjects were considered as disease-associated loci^{24 (link),27 (link),29 (link)}. HM analyses were not carried out in Family ID-Fam04, in which direct WGS to identify the gene defects was performed in the only affected family member.