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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.


Mutation identification of CRB1 gene in the Chinese family and the Indian family and the sporadic Indian patients with arRP.(A) Validation of the CRB1 gene in the family RP-2236. Patients (IV:2, IV:3 and IV:4) harbored the homozygous splicing mutation c.2129-1G>C of the CRB1 gene. The parents (III:1, III:2, III:3, III:4) and the healthy daughter (IV:1) were all unaffected carriers with the heterozygous c.2129-1G>C splicing mutation. (B) Validation of the CRB1 gene in the family RP-IC-90. Patient II:1 harbored the homozygous point mutation p.R764C of the CRB1 gene. The parents (I:1 and I:2) were unaffected carriers with the heterozygous p.R764C mutation. (C) Validation of the CRB1 gene in the sporadic Indian patents. The patient I-44 harbored the homozygous mutation p.G1310C while the patient I-7 harbored the compound heterozygous mutations p.N629D and p.A593T.
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f3: Mutation identification of CRB1 gene in the Chinese family and the Indian family and the sporadic Indian patients with arRP.(A) Validation of the CRB1 gene in the family RP-2236. Patients (IV:2, IV:3 and IV:4) harbored the homozygous splicing mutation c.2129-1G>C of the CRB1 gene. The parents (III:1, III:2, III:3, III:4) and the healthy daughter (IV:1) were all unaffected carriers with the heterozygous c.2129-1G>C splicing mutation. (B) Validation of the CRB1 gene in the family RP-IC-90. Patient II:1 harbored the homozygous point mutation p.R764C of the CRB1 gene. The parents (I:1 and I:2) were unaffected carriers with the heterozygous p.R764C mutation. (C) Validation of the CRB1 gene in the sporadic Indian patents. The patient I-44 harbored the homozygous mutation p.G1310C while the patient I-7 harbored the compound heterozygous mutations p.N629D and p.A593T.

Mentions: Sanger sequencing results showed complete co-segregation of the mutations with the disease phenotype in the consanguineous Chinese family RP-2236 (Table 3). The homozygous splicing mutation c.2129-1G>C in the three affected patients (IV:2, IV:3 and IV:4) was confirmed (Fig. 3). The parents (III:1, III:2, III:3 and III:4) and the daughter (IV:1) were all unaffected carriers with a heterozygous mutation. The c.2129-1G>C splicing mutation in CRB1 results in deletion of exon 7 and is likely to affect the CRB1 protein function dramatically.


Whole exome sequencing identified novel CRB1 mutations in Chinese and Indian populations with autosomal recessive retinitis pigmentosa
Mutation identification of CRB1 gene in the Chinese family and the Indian family and the sporadic Indian patients with arRP.(A) Validation of the CRB1 gene in the family RP-2236. Patients (IV:2, IV:3 and IV:4) harbored the homozygous splicing mutation c.2129-1G>C of the CRB1 gene. The parents (III:1, III:2, III:3, III:4) and the healthy daughter (IV:1) were all unaffected carriers with the heterozygous c.2129-1G>C splicing mutation. (B) Validation of the CRB1 gene in the family RP-IC-90. Patient II:1 harbored the homozygous point mutation p.R764C of the CRB1 gene. The parents (I:1 and I:2) were unaffected carriers with the heterozygous p.R764C mutation. (C) Validation of the CRB1 gene in the sporadic Indian patents. The patient I-44 harbored the homozygous mutation p.G1310C while the patient I-7 harbored the compound heterozygous mutations p.N629D and p.A593T.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5037368&req=5

f3: Mutation identification of CRB1 gene in the Chinese family and the Indian family and the sporadic Indian patients with arRP.(A) Validation of the CRB1 gene in the family RP-2236. Patients (IV:2, IV:3 and IV:4) harbored the homozygous splicing mutation c.2129-1G>C of the CRB1 gene. The parents (III:1, III:2, III:3, III:4) and the healthy daughter (IV:1) were all unaffected carriers with the heterozygous c.2129-1G>C splicing mutation. (B) Validation of the CRB1 gene in the family RP-IC-90. Patient II:1 harbored the homozygous point mutation p.R764C of the CRB1 gene. The parents (I:1 and I:2) were unaffected carriers with the heterozygous p.R764C mutation. (C) Validation of the CRB1 gene in the sporadic Indian patents. The patient I-44 harbored the homozygous mutation p.G1310C while the patient I-7 harbored the compound heterozygous mutations p.N629D and p.A593T.
Mentions: Sanger sequencing results showed complete co-segregation of the mutations with the disease phenotype in the consanguineous Chinese family RP-2236 (Table 3). The homozygous splicing mutation c.2129-1G>C in the three affected patients (IV:2, IV:3 and IV:4) was confirmed (Fig. 3). The parents (III:1, III:2, III:3 and III:4) and the daughter (IV:1) were all unaffected carriers with a heterozygous mutation. The c.2129-1G>C splicing mutation in CRB1 results in deletion of exon 7 and is likely to affect the CRB1 protein function dramatically.

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.