Table 1.
Phenotypes and genetic testing of the eight patients.
Figure 1.
Variant analysis and prioritization workflow.
Summary of our variant evaluation process for identifying candidate mutations
Table 2.
Summary of MPS data for the eight patients.
Figure 2.
L1CAM splice site mutation in Patient 1.
(A) IGV snapshot of c.3458-1G>A variant in the L1CAM gene (Chr X:153129005, hg19). (B) Sanger sequencing confirmation of c.3458-1G>A variant (NM_000425.3) (C) Partial cDNA sequence showing the mutant allele with the 5 bp deletion.
Figure 3.
ATRX p.R2386X mutation in Patient 2.
(A) IGV snapshot of c.7156C>T variant in ATRX (Chr X:76776310, hg19). (B) Sanger sequencing confirmation of c.7156C>T (p.R2386X, NM_00489.3) in Patient 2. (C) Sanger sequencing showing heterozygous c.7156C>T variant in the mother.
Figure 4.
USP9X splice site mutation in Patient 3.
(A) IGV snapshot of c.1986-1G>T variant in USP9X (Chr X:41025124, hg19). (B) Sanger sequencing confirmation of c.1986-1G>T variant (NM_001039590.2) in Patient 3. (C) Partial cDNA sequence showing expression of both the wild type and low level mutant allele with the 13 bp deletion. (D) Partial cDNA sequence of control patient. (E) Partial genomic DNA sequence of exon 15 (uppercase, blue) and intron 14 (lowercase, red) of USP9X gene showing the c.1986-1G>T variant (arrow) and the 13 bp deletion (r.1986_1998delATTTTTATTGAAG) which is underlined.
Table 3.
Assessed candidate variants found in patients 4–8.