PMC3962727_01
Pedigree of an Italian family with choroideremia. Squares and circles indicate males and females, respectively, and the darkened symbols represent the affected members. The patient above the arrow is the proband. Under the symbol (square or circle) of each subject are two rows of information: individual identifier (I:1, I:2, etc.) and genotype for the CHM mutation.
mv-v20-325-f1.jpg
PMC3962727_06_mv-v20-325-f1.jpg
f1
The second child of II:2 was a 7-year-old boy (Figure 1). The patients with CHM were hemizygous, and the female carriers were heterozygous for this mutation (Figure 1 and Figure 6).
Optical coherence tomography, visual field, and fluorescein angiography of the proband and his brother. Widespread chorioretinal atrophy with relative sparing of the macular region and visual field constriction are found. Note the greater severity of the anatomic and functional findings of the proband II:4 (A, B, C) compared to his older brother II:3 (D, E, F). RE,right eye; LE, left eye.
mv-v20-325-f2.jpg
PMC3962727_02_mv-v20-325-f2.jpg
f2
OCT showed normal thickness of the fovea, minimal thinning of the outer retina, and moderate chorioretinal atrophy (Figure 2D). Visual field examination showed an annular scotoma in both eyes (Figure 2E). Fluorescein angiography showed hyper-fluorescence areas in the mid-periphery and in the paramacular region, due to diffuse RPE atrophy (Figure 2F).
Comparison of electroretinography findings of family members. Note the undetectable full-field electroretinography of all responses in the proband (II:4). The dark adapted responses were unrecordable in II:3 and markedly impaired in III:1 and III:2, while the light adapted responses were less compromised. Electrofunctional responses in female carriers (II:2 and I:2) were slightly impaired. RE, right eye; LE, left eye.
mv-v20-325-f3.jpg
PMC3962727_06_mv-v20-325-f3.jpg
f3
The perimetry showed a minor concentric reduction in the visual field, and full-field ERG was less compromised compared to those of his brother (Figure 3 and Figure 4C,D).
PMC3962727_02
Pedigree of an Italian family with choroideremia. Squares and circles indicate males and females, respectively, and the darkened symbols represent the affected members. The patient above the arrow is the proband. Under the symbol (square or circle) of each subject are two rows of information: individual identifier (I:1, I:2, etc.) and genotype for the CHM mutation.
mv-v20-325-f1.jpg
PMC3962727_06_mv-v20-325-f1.jpg
f1
The second child of II:2 was a 7-year-old boy (Figure 1). The patients with CHM were hemizygous, and the female carriers were heterozygous for this mutation (Figure 1 and Figure 6).
Optical coherence tomography, visual field, and fluorescein angiography of the proband and his brother. Widespread chorioretinal atrophy with relative sparing of the macular region and visual field constriction are found. Note the greater severity of the anatomic and functional findings of the proband II:4 (A, B, C) compared to his older brother II:3 (D, E, F). RE,right eye; LE, left eye.
mv-v20-325-f2.jpg
PMC3962727_02_mv-v20-325-f2.jpg
f2
OCT showed normal thickness of the fovea, minimal thinning of the outer retina, and moderate chorioretinal atrophy (Figure 2D). Visual field examination showed an annular scotoma in both eyes (Figure 2E). Fluorescein angiography showed hyper-fluorescence areas in the mid-periphery and in the paramacular region, due to diffuse RPE atrophy (Figure 2F).
Comparison of electroretinography findings of family members. Note the undetectable full-field electroretinography of all responses in the proband (II:4). The dark adapted responses were unrecordable in II:3 and markedly impaired in III:1 and III:2, while the light adapted responses were less compromised. Electrofunctional responses in female carriers (II:2 and I:2) were slightly impaired. RE, right eye; LE, left eye.
mv-v20-325-f3.jpg
PMC3962727_06_mv-v20-325-f3.jpg
f3
The perimetry showed a minor concentric reduction in the visual field, and full-field ERG was less compromised compared to those of his brother (Figure 3 and Figure 4C,D).
PMC3962727_03
Comparison of electroretinography findings of family members. Note the undetectable full-field electroretinography of all responses in the proband (II:4). The dark adapted responses were unrecordable in II:3 and markedly impaired in III:1 and III:2, while the light adapted responses were less compromised. Electrofunctional responses in female carriers (II:2 and I:2) were slightly impaired. RE, right eye; LE, left eye.
mv-v20-325-f3.jpg
PMC3962727_06_mv-v20-325-f3.jpg
f3
The perimetry showed a minor concentric reduction in the visual field, and full-field ERG was less compromised compared to those of his brother (Figure 3 and Figure 4C,D).
PMC3962727_04
Comparison of electroretinography findings of family members. Note the undetectable full-field electroretinography of all responses in the proband (II:4). The dark adapted responses were unrecordable in II:3 and markedly impaired in III:1 and III:2, while the light adapted responses were less compromised. Electrofunctional responses in female carriers (II:2 and I:2) were slightly impaired. RE, right eye; LE, left eye.
mv-v20-325-f3.jpg
PMC3962727_06_mv-v20-325-f3.jpg
f3
The perimetry showed a minor concentric reduction in the visual field, and full-field ERG was less compromised compared to those of his brother (Figure 3 and Figure 4C,D).
PMC3962727_05
Pedigree of an Italian family with choroideremia. Squares and circles indicate males and females, respectively, and the darkened symbols represent the affected members. The patient above the arrow is the proband. Under the symbol (square or circle) of each subject are two rows of information: individual identifier (I:1, I:2, etc.) and genotype for the CHM mutation.
mv-v20-325-f1.jpg
PMC3962727_06_mv-v20-325-f1.jpg
f1
The second child of II:2 was a 7-year-old boy (Figure 1). The patients with CHM were hemizygous, and the female carriers were heterozygous for this mutation (Figure 1 and Figure 6).
Comparison of electroretinography findings of family members. Note the undetectable full-field electroretinography of all responses in the proband (II:4). The dark adapted responses were unrecordable in II:3 and markedly impaired in III:1 and III:2, while the light adapted responses were less compromised. Electrofunctional responses in female carriers (II:2 and I:2) were slightly impaired. RE, right eye; LE, left eye.
mv-v20-325-f3.jpg
PMC3962727_06_mv-v20-325-f3.jpg
f3
The perimetry showed a minor concentric reduction in the visual field, and full-field ERG was less compromised compared to those of his brother (Figure 3 and Figure 4C,D).
Fundus photography and perimetry of the two children. Retinal pigment epithelium mid-periphery pigment changes are already visible. Perimetry shows concentric reduction in the visual field in patient III:1 (A, B) and patient III:2 (C, D). RE, right eye; LE, left eye.
mv-v20-325-f4.jpg
PMC3962727_06_mv-v20-325-f4.jpg
f4
The perimetry showed a minor concentric reduction in the visual field, and full-field ERG was less compromised compared to those of his brother (Figure 3 and Figure 4C,D).
PMC3962727_06
Pedigree of an Italian family with choroideremia. Squares and circles indicate males and females, respectively, and the darkened symbols represent the affected members. The patient above the arrow is the proband. Under the symbol (square or circle) of each subject are two rows of information: individual identifier (I:1, I:2, etc.) and genotype for the CHM mutation.
mv-v20-325-f1.jpg
PMC3962727_06_mv-v20-325-f1.jpg
f1
The second child of II:2 was a 7-year-old boy (Figure 1). The patients with CHM were hemizygous, and the female carriers were heterozygous for this mutation (Figure 1 and Figure 6).
Comparison of electroretinography findings of family members. Note the undetectable full-field electroretinography of all responses in the proband (II:4). The dark adapted responses were unrecordable in II:3 and markedly impaired in III:1 and III:2, while the light adapted responses were less compromised. Electrofunctional responses in female carriers (II:2 and I:2) were slightly impaired. RE, right eye; LE, left eye.
mv-v20-325-f3.jpg
PMC3962727_06_mv-v20-325-f3.jpg
f3
The perimetry showed a minor concentric reduction in the visual field, and full-field ERG was less compromised compared to those of his brother (Figure 3 and Figure 4C,D).
Fundus photography and perimetry of the two children. Retinal pigment epithelium mid-periphery pigment changes are already visible. Perimetry shows concentric reduction in the visual field in patient III:1 (A, B) and patient III:2 (C, D). RE, right eye; LE, left eye.
mv-v20-325-f4.jpg
PMC3962727_06_mv-v20-325-f4.jpg
f4
The perimetry showed a minor concentric reduction in the visual field, and full-field ERG was less compromised compared to those of his brother (Figure 3 and Figure 4C,D).
Immunoblot analysis of the Rab escort protein-1 protein from patients II:4 (2, 9), II:3 (3, 10), III:1 e III:2 (5, 6); from the female carrier II:2 (4, 8); from the normal controls: male (1) and female (7); lane 11: ladder in the range of 20-220 kDa (MagicMark XP Western Protein Standard) and female (7, 11).
mv-v20-325-f5.jpg
PMC3962727_06_mv-v20-325-f5.jpg
f5
LCLs from the CHM proband (II:4) and the other affected men (II:3, III:1, III:2) did not show detectable amounts of normal REP-1 protein but a smaller protein band (also present in the female carrier) and probably corresponding to a shorter translational product of REP-1 (Figure 5).
A novel splice-site mutation of CHM gene. A: Mutation analysis of CHM gene performed by direct sequencing on genomic DNA from patient II:4 showed a new mutation c.819+2T>A. B: The female carrier II:2 resulted heterozygous for the mutation c.819+2T>A. C: Mutation analysis of CHM gene performed by RT-PCR in mRNA from the proband (line 3), female carrier II:2 (line 4), wild type male (line 2), Ladder 100 bp (line 1) and negative reaction control (line 5). D: Sequencing analysis of the 394 bp cDNA reverse transcripted from mRNA patient II:4 show that the whole exon 6 is deleted as result of splicing mutation c.819+2T>A. E: Consequence of CHM gene splicing mutation c.819+2T>A on mRNA.
mv-v20-325-f6.jpg
PMC3962727_06_mv-v20-325-f6.jpg
f6
The patients with CHM were hemizygous, and the female carriers were heterozygous for this mutation (Figure 1 and Figure 6). The sequence analysis of the excised band from patient II:4 revealed only one aberrantly spliced mRNA lacking exon 6 and the absence of a normal transcript, while cDNA from carrier II:2 showed the presence of normal and mutated transcripts (Figure 6).