#619845
Table of Contents
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-93 (RP93) is caused by compound heterozygous mutation in the CC2D2A gene (612013) on chromosome 4p15.
Retinitis pigmentosa-93 (RP93) is characterized by mild to moderate rod-cone dystrophy with onset in the second or third decade of life. Patients have constricted visual fields with macular sparing and show mildly reduced visual acuity with mild to high myopia (Mejecase et al., 2019).
For a general phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
Mejecase et al. (2019) reported 3 brothers, born of consanguineous Senegalese parents, with retinitis pigmentosa and mutation in the CC2D2A gene. The 2 older brothers (CIC02584 and CIC03585) had mild to moderate rod-cone dystrophy diagnosed at ages 19 years and 25 years, respectively, with best corrected visual acuities (BCVAs) of 20/32 bilaterally and mild to high myopia. They had moderately constricted visual fields and undetectable responses on full-field electroretinography (ff-ERG). Fundus examination and autofluorescence as well as spectral-domain optical coherence tomography (SD-OCT) were consistent with rod-cone dystrophy, with preserved maculae bilaterally. The proband (CIC02583), who was the most severely affected brother, experienced marked photophobia, congenital nystagmus, and poor vision since birth. His BCVA progressively worsened, to only light-perception by age 21 years. Visual fields were severely constricted and ff-ERG responses were undetectable. Fundus examination and autofluorescence and SD-OCT documented severe macular alteration in addition to peripheral changes. The 2 younger brothers also had proteinuria, and the youngest also had hypertension and hematuria. None of the brothers had impaired intellectual development, and brain MRIs were normal, with no sign of cerebellar vermis hypoplasia.
The transmission pattern of retinitis pigmentosa in the family reported by Mejecase et al. (2019) was consistent with autosomal recessive inheritance.
In the oldest affected brother (CIC02584) from a Senegalese family with retinitis pigmentosa, Mejecase et al. (2019) screened a next-generation sequencing (NGS) panel of 120 RP-associated genes and did not find any pathogenic variants. Whole-exome and Sanger sequencing in the 3 affected brothers revealed compound heterozygosity for a missense mutation (R925P; 612013.0010) and a deletion/insertion (612013.0011) in the CC2D2A gene. Analysis of targeted NGS data from 1,056 cases of nonsyndromic retinal dystrophy identified a 36-year-old woman from Central Africa who was compound heterozygous for the R925P mutation and a 16,145-bp deletion (612013.0012) in the CC2D2A gene. In 2 of the Senegalese brothers who also had proteinuria, the authors identified compound heterozygosity for a nonsense and a missense mutation in CUBN (602997), a gene associated with chronic benign proteinuria (618884). In addition, the youngest brother, who had the most severe ocular phenotype, was found to be homozygous for a frameshift mutation in the achromatopsia-associated CNGA3 gene (600053.0011), which likely accounted for his early-onset cone dysfunction (ACHM2; 216900). The respective variants segregated fully with disease in the Senegalese family, and the authors noted that this case report illustrated the power of whole-exome sequencing to elucidate complex phenotypes segregating within a family.
Mejecase, C., Hummel, A., Mohand-Said, S., Andrieu, C., El Shamieh, S., Antonio, A., Condroyer, C., Boyard, F., Foussard, M., Blanchard, S., Letexier, M., Saraiva,, J.-P., Sahel, J.-A., Zeitz, C., Audo, I. Whole exome sequencing resolves complex phenotype and identifies CC2D2A mutations underlying non-syndromic rod-cone dystrophy. Clin. Genet. 95: 329-333, 2019. [PubMed: 30267408, related citations] [Full Text]
ORPHA: 791;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 4p15.32 | Retinitis pigmentosa 93 | 619845 | Autosomal recessive | 3 | CC2D2A | 612013 |
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-93 (RP93) is caused by compound heterozygous mutation in the CC2D2A gene (612013) on chromosome 4p15.
Retinitis pigmentosa-93 (RP93) is characterized by mild to moderate rod-cone dystrophy with onset in the second or third decade of life. Patients have constricted visual fields with macular sparing and show mildly reduced visual acuity with mild to high myopia (Mejecase et al., 2019).
For a general phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
Mejecase et al. (2019) reported 3 brothers, born of consanguineous Senegalese parents, with retinitis pigmentosa and mutation in the CC2D2A gene. The 2 older brothers (CIC02584 and CIC03585) had mild to moderate rod-cone dystrophy diagnosed at ages 19 years and 25 years, respectively, with best corrected visual acuities (BCVAs) of 20/32 bilaterally and mild to high myopia. They had moderately constricted visual fields and undetectable responses on full-field electroretinography (ff-ERG). Fundus examination and autofluorescence as well as spectral-domain optical coherence tomography (SD-OCT) were consistent with rod-cone dystrophy, with preserved maculae bilaterally. The proband (CIC02583), who was the most severely affected brother, experienced marked photophobia, congenital nystagmus, and poor vision since birth. His BCVA progressively worsened, to only light-perception by age 21 years. Visual fields were severely constricted and ff-ERG responses were undetectable. Fundus examination and autofluorescence and SD-OCT documented severe macular alteration in addition to peripheral changes. The 2 younger brothers also had proteinuria, and the youngest also had hypertension and hematuria. None of the brothers had impaired intellectual development, and brain MRIs were normal, with no sign of cerebellar vermis hypoplasia.
The transmission pattern of retinitis pigmentosa in the family reported by Mejecase et al. (2019) was consistent with autosomal recessive inheritance.
In the oldest affected brother (CIC02584) from a Senegalese family with retinitis pigmentosa, Mejecase et al. (2019) screened a next-generation sequencing (NGS) panel of 120 RP-associated genes and did not find any pathogenic variants. Whole-exome and Sanger sequencing in the 3 affected brothers revealed compound heterozygosity for a missense mutation (R925P; 612013.0010) and a deletion/insertion (612013.0011) in the CC2D2A gene. Analysis of targeted NGS data from 1,056 cases of nonsyndromic retinal dystrophy identified a 36-year-old woman from Central Africa who was compound heterozygous for the R925P mutation and a 16,145-bp deletion (612013.0012) in the CC2D2A gene. In 2 of the Senegalese brothers who also had proteinuria, the authors identified compound heterozygosity for a nonsense and a missense mutation in CUBN (602997), a gene associated with chronic benign proteinuria (618884). In addition, the youngest brother, who had the most severe ocular phenotype, was found to be homozygous for a frameshift mutation in the achromatopsia-associated CNGA3 gene (600053.0011), which likely accounted for his early-onset cone dysfunction (ACHM2; 216900). The respective variants segregated fully with disease in the Senegalese family, and the authors noted that this case report illustrated the power of whole-exome sequencing to elucidate complex phenotypes segregating within a family.
Mejecase, C., Hummel, A., Mohand-Said, S., Andrieu, C., El Shamieh, S., Antonio, A., Condroyer, C., Boyard, F., Foussard, M., Blanchard, S., Letexier, M., Saraiva,, J.-P., Sahel, J.-A., Zeitz, C., Audo, I. Whole exome sequencing resolves complex phenotype and identifies CC2D2A mutations underlying non-syndromic rod-cone dystrophy. Clin. Genet. 95: 329-333, 2019. [PubMed: 30267408] [Full Text: https://doi.org/10.1111/cge.13453]
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