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Whole exome sequencing identified novel CRB1 mutations in Chinese and Indian populations with autosomal recessive retinitis pigmentosa

View Article: PubMed Central - PubMed

ABSTRACT

Retinitis pigmentosa (RP) is a leading cause of inherited blindness characterized by progressive degeneration of the retinal photoreceptor cells. This study aims to identify genetic mutations in a Chinese family RP-2236, an Indian family RP-IC-90 and 100 sporadic Indian individuals with autosomal recessive RP (arRP). Whole exome sequencing was performed on the index patients of RP-2236, RP-IC-90 and all of the 100 sporadic Indian patients. Direct Sanger sequencing was used to validate the mutations identified. Four novel mutations and one reported mutation in the crumbs homolog 1 (CRB1) gene, which has been known to cause severe retinal dystrophies, were identified. A novel homozygous splicing mutation c.2129-1G>C was found in the three patients In family RP-2236. A homozygous point mutation p.R664C was found in RP-IC-90. A novel homozygous mutation p.G1310C was identified in patient I-44, while novel compound heterozygous mutations p.N629D and p.A593T were found in patient I-7. All mutations described above were not present in the 1000 normal controls. In conclusion, we identified four novel mutations in CRB1 in a cohort of RP patients from the Chinese and Indian populations. Our data enlarges the CRB1 mutation spectrums and may provide new target loci for RP diagnose and treatment.

No MeSH data available.


Pedigrees of the Chinese and Indian family with arRP.Arrow indicated the proband patient IV:2 in the Chinese family of RP-2236 (A) and the proband patient II:1 in the Indian family of RP-IC-90 (B). Solid symbol indicated affected individual while open symbols indicated unaffected individuals.
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f1: Pedigrees of the Chinese and Indian family with arRP.Arrow indicated the proband patient IV:2 in the Chinese family of RP-2236 (A) and the proband patient II:1 in the Indian family of RP-IC-90 (B). Solid symbol indicated affected individual while open symbols indicated unaffected individuals.

Mentions: A Chinese family with three patients affected with retinitis pigmentosa, an Indian family with one patient affected with retinitis pigmentosa, 100 sporadic Indian RP patients and 1000 normal control were recruited in the study (Fig. 1). All of the RP patients presented typical RP clinical features, including early-onset increasing difficulty to adapt in the dark, gradually decreased vision acuity, and lost of peripheral and subsequent central visual field. The clinical examination of patient IV:2 in the Chinese family RP-2236 was shown in Fig. 2. Fundus examination showed the loss of pigment epithelial with narrowed arterioles, pale optic disk and irregular pigment clumps with both peripheral retina and macula involved in both eyes (Fig. 2A). The FFA showed extensive transmitted and blocked fluorescence due to loss of pigment epithelium with scattered pigment clumps (Fig. 2B). Both of the mfERG and full field ERG showed weak response under both scotopic and photopic condition, especially at the peripheral retina, indicating significant loss of function of both rods and cones (Fig. 2C and Supplementary Figure S1). Fundus photography of the other two patients in the family also showed similar changes to patient IV:2 (Supplementary Figure S2) The Indian RP patients and the normal controls recruited in this study also received complete ophthalmological examinations.


Whole exome sequencing identified novel CRB1 mutations in Chinese and Indian populations with autosomal recessive retinitis pigmentosa
Pedigrees of the Chinese and Indian family with arRP.Arrow indicated the proband patient IV:2 in the Chinese family of RP-2236 (A) and the proband patient II:1 in the Indian family of RP-IC-90 (B). Solid symbol indicated affected individual while open symbols indicated unaffected individuals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037368&req=5

f1: Pedigrees of the Chinese and Indian family with arRP.Arrow indicated the proband patient IV:2 in the Chinese family of RP-2236 (A) and the proband patient II:1 in the Indian family of RP-IC-90 (B). Solid symbol indicated affected individual while open symbols indicated unaffected individuals.
Mentions: A Chinese family with three patients affected with retinitis pigmentosa, an Indian family with one patient affected with retinitis pigmentosa, 100 sporadic Indian RP patients and 1000 normal control were recruited in the study (Fig. 1). All of the RP patients presented typical RP clinical features, including early-onset increasing difficulty to adapt in the dark, gradually decreased vision acuity, and lost of peripheral and subsequent central visual field. The clinical examination of patient IV:2 in the Chinese family RP-2236 was shown in Fig. 2. Fundus examination showed the loss of pigment epithelial with narrowed arterioles, pale optic disk and irregular pigment clumps with both peripheral retina and macula involved in both eyes (Fig. 2A). The FFA showed extensive transmitted and blocked fluorescence due to loss of pigment epithelium with scattered pigment clumps (Fig. 2B). Both of the mfERG and full field ERG showed weak response under both scotopic and photopic condition, especially at the peripheral retina, indicating significant loss of function of both rods and cones (Fig. 2C and Supplementary Figure S1). Fundus photography of the other two patients in the family also showed similar changes to patient IV:2 (Supplementary Figure S2) The Indian RP patients and the normal controls recruited in this study also received complete ophthalmological examinations.

View Article: PubMed Central - PubMed

ABSTRACT

Retinitis pigmentosa (RP) is a leading cause of inherited blindness characterized by progressive degeneration of the retinal photoreceptor cells. This study aims to identify genetic mutations in a Chinese family RP-2236, an Indian family RP-IC-90 and 100 sporadic Indian individuals with autosomal recessive RP (arRP). Whole exome sequencing was performed on the index patients of RP-2236, RP-IC-90 and all of the 100 sporadic Indian patients. Direct Sanger sequencing was used to validate the mutations identified. Four novel mutations and one reported mutation in the crumbs homolog 1 (CRB1) gene, which has been known to cause severe retinal dystrophies, were identified. A novel homozygous splicing mutation c.2129-1G>C was found in the three patients In family RP-2236. A homozygous point mutation p.R664C was found in RP-IC-90. A novel homozygous mutation p.G1310C was identified in patient I-44, while novel compound heterozygous mutations p.N629D and p.A593T were found in patient I-7. All mutations described above were not present in the 1000 normal controls. In conclusion, we identified four novel mutations in CRB1 in a cohort of RP patients from the Chinese and Indian populations. Our data enlarges the CRB1 mutation spectrums and may provide new target loci for RP diagnose and treatment.

No MeSH data available.