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Developmental or degenerative--NR2E3 gene mutations in two patients with enhanced S cone syndrome.

Udar N, Small K, Chalukya M, Silva-Garcia R, Marmor M - Mol. Vis. (2011)

Bottom Line: Case 2, with more traditional Goldmann-Favre Syndrome with retinal degeneration, was a compound heterozygote where one allele had a similar P-box deletion but the other was a splicing defect.Case 1 is the first reported homozygous deletion within the P-box.This is the first report of NR2E3 mutations in a Persian and a Brazilian family.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, University of California Irvine, Irvine, CA, USA.

ABSTRACT

Purpose: Enhanced S Cone Syndrome is a rare autosomal recessive disorder characterized clinically by an absence of rod function, a replacement of most L and M cone function by S cone activity (Goldmann-Favre Syndrome) and by variable degrees of retinal degeneration in different families. The causative gene, nuclear receptor subfamily 2, group E, member 3 (NR2E3), controls the developmental sequence for rods and cones. The purpose of this study was to compare the nature and implications of mutations in two subjects with Enhanced S Cone Syndrome who have significantly different degrees of degenerative damage.

Methods: A direct sequencing approach was used to identify the mutations. Genomic DNA was amplified from all the exons of NR2E3 and used as a template for sequencing. Of the two families studied, Case 1 is of Persian ethnicity while Case 2 is Brazilian. A total of six individuals within the two families were studied.

Results: Case 1 (original propositus of the syndrome) has the characteristic developmental rod/cone abnormality with large amplitude electroretinogram responses and no retinal degeneration. She was homozygous for a novel mutation, c.[del196-201del6] (p.G66-C67del), which lies entirely within the P-box for this gene. By comparison, Case 2 had Goldmann-Favre Syndrome with retinal degeneration and low electroretinogram signals. She was a compound heterozygote for c.[119-2A>C]+[del194-202del9] (p.N65-C67del), mutations that have been reported previously. Her second mutation overlaps that of Case 1 within the P-box.

Conclusions: The novel in-frame homozygous deletion of Case 1, within the P-box motif of the DNA binding domain, caused a developmental abnormality without retinal degeneration. Case 2, with more traditional Goldmann-Favre Syndrome with retinal degeneration, was a compound heterozygote where one allele had a similar P-box deletion but the other was a splicing defect. Case 1 is the first reported homozygous deletion within the P-box. This is the first report of NR2E3 mutations in a Persian and a Brazilian family.

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DNA sequencing of the NR2E3 gene in family 1 with the propositus #2743 showing the homozygous deletion. Pedigree: + - indicate individual that have been examined. Black solid fill ● – affected phenotype. White solid fill □ – normal phenotype. Pattern filled square and circle– individual assumed carrier. # - Sample Number.
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f2: DNA sequencing of the NR2E3 gene in family 1 with the propositus #2743 showing the homozygous deletion. Pedigree: + - indicate individual that have been examined. Black solid fill ● – affected phenotype. White solid fill □ – normal phenotype. Pattern filled square and circle– individual assumed carrier. # - Sample Number.

Mentions: After amplification of all exons of NR2E3, we sequenced them for patient #2743. Using these data, we identified a homozygous in-frame deletion mutation c.del196–201del6 (p.G66-C67del; Figure 2). We amplified exon 2 for all three family members (parents #3385, #3387 and brother #3386; Figure 2). None of the family members had the ESCS phenotype. DNA sequencing results revealed that both the parents (#3385 and #3387) were heterozygous for the mutation (data not shown). The patient’s brother (#3386) was negative for the mutation (data not shown), suggesting that he inherited the normal allele from both parents. As shown in Figure 3, this novel mutation is located within the conserved P-box of the DNA binding domain.


Developmental or degenerative--NR2E3 gene mutations in two patients with enhanced S cone syndrome.

Udar N, Small K, Chalukya M, Silva-Garcia R, Marmor M - Mol. Vis. (2011)

DNA sequencing of the NR2E3 gene in family 1 with the propositus #2743 showing the homozygous deletion. Pedigree: + - indicate individual that have been examined. Black solid fill ● – affected phenotype. White solid fill □ – normal phenotype. Pattern filled square and circle– individual assumed carrier. # - Sample Number.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3044695&req=5

f2: DNA sequencing of the NR2E3 gene in family 1 with the propositus #2743 showing the homozygous deletion. Pedigree: + - indicate individual that have been examined. Black solid fill ● – affected phenotype. White solid fill □ – normal phenotype. Pattern filled square and circle– individual assumed carrier. # - Sample Number.
Mentions: After amplification of all exons of NR2E3, we sequenced them for patient #2743. Using these data, we identified a homozygous in-frame deletion mutation c.del196–201del6 (p.G66-C67del; Figure 2). We amplified exon 2 for all three family members (parents #3385, #3387 and brother #3386; Figure 2). None of the family members had the ESCS phenotype. DNA sequencing results revealed that both the parents (#3385 and #3387) were heterozygous for the mutation (data not shown). The patient’s brother (#3386) was negative for the mutation (data not shown), suggesting that he inherited the normal allele from both parents. As shown in Figure 3, this novel mutation is located within the conserved P-box of the DNA binding domain.

Bottom Line: Case 2, with more traditional Goldmann-Favre Syndrome with retinal degeneration, was a compound heterozygote where one allele had a similar P-box deletion but the other was a splicing defect.Case 1 is the first reported homozygous deletion within the P-box.This is the first report of NR2E3 mutations in a Persian and a Brazilian family.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, University of California Irvine, Irvine, CA, USA.

ABSTRACT

Purpose: Enhanced S Cone Syndrome is a rare autosomal recessive disorder characterized clinically by an absence of rod function, a replacement of most L and M cone function by S cone activity (Goldmann-Favre Syndrome) and by variable degrees of retinal degeneration in different families. The causative gene, nuclear receptor subfamily 2, group E, member 3 (NR2E3), controls the developmental sequence for rods and cones. The purpose of this study was to compare the nature and implications of mutations in two subjects with Enhanced S Cone Syndrome who have significantly different degrees of degenerative damage.

Methods: A direct sequencing approach was used to identify the mutations. Genomic DNA was amplified from all the exons of NR2E3 and used as a template for sequencing. Of the two families studied, Case 1 is of Persian ethnicity while Case 2 is Brazilian. A total of six individuals within the two families were studied.

Results: Case 1 (original propositus of the syndrome) has the characteristic developmental rod/cone abnormality with large amplitude electroretinogram responses and no retinal degeneration. She was homozygous for a novel mutation, c.[del196-201del6] (p.G66-C67del), which lies entirely within the P-box for this gene. By comparison, Case 2 had Goldmann-Favre Syndrome with retinal degeneration and low electroretinogram signals. She was a compound heterozygote for c.[119-2A>C]+[del194-202del9] (p.N65-C67del), mutations that have been reported previously. Her second mutation overlaps that of Case 1 within the P-box.

Conclusions: The novel in-frame homozygous deletion of Case 1, within the P-box motif of the DNA binding domain, caused a developmental abnormality without retinal degeneration. Case 2, with more traditional Goldmann-Favre Syndrome with retinal degeneration, was a compound heterozygote where one allele had a similar P-box deletion but the other was a splicing defect. Case 1 is the first reported homozygous deletion within the P-box. This is the first report of NR2E3 mutations in a Persian and a Brazilian family.

Show MeSH
Related in: MedlinePlus