Specific combination of compound heterozygous mutations in 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4) defines a new subtype of D-bifunctional protein deficiency

Table 3 Filtering of exome sequencing variants

Genes with missense, nonsense, indel or splice variants	6453
Genes with rare mutations¹	372
Genes with mutations shared by siblings	109
Genes with homozygous/ multiple heterozygous mutations	2²

¹Variants were filtered out if they had a minor allele frequency (MAF) >0.01 in the 1000 genomes database, the NHLBI exome server or were seen in >2 of 435 control exomes sequenced at our center.
²The 2 genes were C16orf82 and FAM83C; these genes were rejected as candidates since two control samples possessed identical sequence variants in C16orf82 and one control sample possessed an identical sequence variant in FAM83C. The 109 genes with at least one mutation shared by the siblings were then re-examined and the HSD17B4 mutations were identified. The second HSD17B4 mutation was not initially identified in Patient 2 due to low coverage (given presence in only 2/8 reads it was given a variant quality of 18.4 which is below our threshold of 20).

ISSN: 1750-1172