Thirty-eight truncating variants observed in the 702 genes from the X-specific part of the X chromosome were each found in only a single XLMR-affected family (that is, they were nonrecurrent variants). One gene (CUL4B) had five different nonrecurrent truncating variants, two genes (AP1S2 and UPF3B) had three, four genes (BRWD3, ZDHHC9, ITIH5L, SLC9A6) had two, and 19 genes had a single nonrecurrent truncating variant (Table 3 and Supplementary Fig. 1 online). Simulating a random distribution of truncating variants through the 702 genes and comparing it to the distribution observed provided strong evidence for clustering of these nonrecurrent truncating variants (P < 0.001) in a subset of genes. The clustering is consistent with this subset of genes being involved in XLMR, but other explanations cannot be excluded at this stage of analysis.
