Whole-exome sequencing in a case of congenital generalized hypertrichosis terminalis (CGHT) revealed a splice site mutation in ABCA5.

(A) Clinical photos of proband that illustrate the excessive hair overgrowth on the back (upper photo) and leg (lower photo). The proband is two years of age in this photo. (B) Pedigree of the family from a consanguineous union (indicated by double lines), where the proband (arrow) is the only affected member. Asterisks indicate the individuals on whom whole-exome sequencing was performed. (C) Quantification of the length (mm) of patient versus control hair follicles derived from the forearm revealed that patient hair follicles are 87% longer, with an average length of 29.6 mm (±0.9 mm) compared to 15.9 mm (±0.6 mm) for control follicles (***P<0.0001). (D) Whole-exome sequencing filtering strategy, including the number of alterations and genes obtained at each level. One alteration (c.4320+1G>C) was identified in the ABCA5 gene, and cosegregation analysis in the family members revealed that both parents are carriers of this mutation, whereas the two unaffected sisters do not carry this mutation. (E) View of ABCA5 (red) and the surrounding genes (black boxes) on chr17q24.2-q24.3, where arrows indicate direction of transcription. A magnified view of the c.4320+1G>C mutation in exon 32 of ABCA5 with the exon 32-intron 32 boundary reference sequence annotated in colors corresponding to sequencing peaks. The G>C substitution is indicated below the control sequence. (F) Sequencing of control, carrier, and affected genomic DNA confirmed heterozygosity for the c.4320+1G>C mutation (boxed) in the father (I-1) and homozygosity in the proband (II-1). All coordinates reference the UCSC Genome Browser human reference genome hg19.