Pedigree of the three families in this study with novel <i>CYP4V2</i> mutation c.219T>A (p.F73L).

<p>(A) Pedigree of family 7 (F7 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094960#pone-0094960-t001" target="_blank">Table 1</a>). (B) Pedigree of family 10 (F10 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094960#pone-0094960-t001" target="_blank">Table 1</a>). (C) Pedigree of family 12 (F12 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094960#pone-0094960-t001" target="_blank">Table 1</a>). Squares, males; circles, females; filled squares or circles, affected family members; slash, deceased family member; arrow, proband; asterisk, a study participant from whom a blood sample was obtained.</p

Spectral domain-optical coherence tomography (SD-OCT) image of BCD with outer retinal tubulation (ORT, white arrows).

<p>(A) SD-OCT of right eye of patient P1. (B) SD-OCT of right eye of patient P3.</p

Summary of clinical and genetic features in patients with <i>CYP4V2</i> mutations

<p>BCVA, best corrected visual acuity; RE, right eye; LE, left eye; M, male; F, female; FC, finger count.</p

Fundus manifestations of three probands with the novel <i>CYP4V2</i> mutation (p.F73L) identified in this study.

<p>(A) Right eye of patient P7. (B) Right eye of patient P10. (C) Left eye of patient P12.1.</p

Multiple sequence alignment for CYP4V2 (partially).

<p>The phenylalanine residue at position 73 (rectangle) is highly conserved across primates and other vertebrates.</p

Ocular phenotype of patient P6.1.

<p>(A) Fundus photograph of right eye shows crystalline deposits with retinal pigment epithelium (RPE) and choriocapillaris atrophy and macular hole. (B) Late phase of fundus fluorescein angiography (FFA) of right eye shows choriocapillaris-RPE complex atrophy, while macular leakage is not shown. (<b>C</b>) Spectral domain-optical coherence tomography (SD-OCT) of right eye shows a lamellar hole attributable to macular cysts. (D) Fundus photograph of left eye shows crystalline deposits with RPE and choriocapillaris atrophy. (E) Late phase of FFA of left eye shows choriocapillaris-RPE complex atrophy, while partial reservation of choriocapillaris in macular is noted (white arrow). (F) SD-OCT of left eye shows thinning of the neuroretina, disturbed organization of the RPE-photoreceptor outer/inner segment layer, increased backscatter, and intraretinal hyperrefractive spot related to crystalline deposit (white arrow).</p

Identification of the <i>CYP4V2</i> c.219T>A mutation.

<p>Partial DNA sequence of <i>CYP4V2</i> exon 2 in DNA from three probands and a control subject. (A) Arrow shows a heterozygous T to A transition at nucleotide position 219 in patient P10. (B) and (C) Arrow shows a homozygous T to A transition at nucleotide position 219 in patient P7 and patient P12.1, respectively. (D) Arrow shows normal base at nucleotide position 219 in the control subject.</p

Ocular phenotype of patient P9 at initial examination.

<p>(A) Fundus photograph of right eye shows crystalline deposits with retinal pigment epithelium (RPE) atrophy. (B) Fundus photograph of left eye shows crystalline deposits with RPE atrophy, active choroidal neovascularization (CNV), and subretinal hemorrhage (white arrow). (C) Late phase of fundus fluorescein angiography (FFA) of right eye shows scattered hypofluorescent areas due to choriocapillaris filling defects, surrounded by areas of hyperfluorescent RPE window defects. (D) FFA of left eye shows central hyperfluorescence (leaked fluorescein) in the late phase, suggestive of active CNV. (E) Spectral domain-optical coherence tomography (SD-OCT) of right eye shows disturbed organization of the RPE-photoreceptor outer/inner segment layer. (F) SD-OCT of left eye shows a subfoveal hyperreflective pre-epithelial lesion and macular edema, suggestive of active CNV.</p

Summary of clinical features in patients with <i>CYP4V2</i> mutations

<p>BE, both eyes; RE, right eye; LE, left eye; CD, crystalline deposits; RA, retinal pigment epithelium atrophy; CA, choriocapillaris atrophy; RVA, retinal vascular attenuation; PC, pigment clumping.</p