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Targeted next generation sequencing identifies novel mutations in RP1 as a relatively common cause of autosomal recessive rod-cone dystrophy.

El Shamieh S, Boulanger-Scemama E, Lancelot ME, Antonio A, Démontant V, Condroyer C, Letexier M, Saraiva JP, Mohand-Saïd S, Sahel JA, Audo I, Zeitz C - Biomed Res Int (2015)

Bottom Line: Eight of the mutations were novel, and all cosegregated with severe arRCD phenotype, found associated with additional macular changes.Among the identified mutations, 4 belong to a region, previously associated with arRCD, and 5 others in a region previously associated with adRCD.These results point out for the necessity of sequencing RP1 when genetically investigating sporadic and arRCD.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U968, 75012 Paris, France ; Sorbonne Universités, UPMC University, Paris 06, UMR_S 968, Institut de la Vision, 75012 Paris, France ; CNRS, UMR_7210, 75012 Paris, France.

ABSTRACT
We report ophthalmic and genetic findings in families with autosomal recessive rod-cone dystrophy (arRCD) and RP1 mutations. Detailed ophthalmic examination was performed in 242 sporadic and arRCD subjects. Genomic DNA was investigated using our customized next generation sequencing panel targeting up to 123 genes implicated in inherited retinal disorders. Stringent filtering coupled with Sanger sequencing and followed by cosegregation analysis was performed to confirm biallelism and the implication of the most likely disease causing variants. Sequencing identified 9 RP1 mutations in 7 index cases. Eight of the mutations were novel, and all cosegregated with severe arRCD phenotype, found associated with additional macular changes. Among the identified mutations, 4 belong to a region, previously associated with arRCD, and 5 others in a region previously associated with adRCD. Our prevalence studies showed that RP1 mutations account for up to 2.5% of arRCD. These results point out for the necessity of sequencing RP1 when genetically investigating sporadic and arRCD. It further highlights the interest of unbiased sequencing technique, which allows investigating the implication of the same gene in different modes of inheritance. Finally, it reports that different regions of RP1 can also lead to arRCD.

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Related in: MedlinePlus

Pedigrees of seven families with RP1 mutations underlying autosomal recessive rod-cone dystrophy. Affected and unaffected individuals are represented by shapes filled with black and white colors, respectively. Men and women are indicated by squares and circles, respectively. Index subjects are marked by ↖. Consanguinity is marked by a double horizontal line.
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fig3: Pedigrees of seven families with RP1 mutations underlying autosomal recessive rod-cone dystrophy. Affected and unaffected individuals are represented by shapes filled with black and white colors, respectively. Men and women are indicated by squares and circles, respectively. Index subjects are marked by ↖. Consanguinity is marked by a double horizontal line.

Mentions: Patient family F303: II.1 (CIC00445) was found to carry compound heterozygous variants: a nonsense mutation c.1625C>G, leading to a predicted premature stop (p.Ser542*) and a deletion c.4587_4590delTAAG leading to a frameshift and a premature termination codon (p.Ser1529Argfs*9) (Table 2, Figure 3). Patient family F752: II.1 (CIC01245) was also found to carry compound heterozygous variants: a 1 bp duplication c.2025dupA leading to p.Ser676Ilefs*22 and a 1 bp deletion c.2377delA leading to p.Arg793Glufs*55 (Table 2).


Targeted next generation sequencing identifies novel mutations in RP1 as a relatively common cause of autosomal recessive rod-cone dystrophy.

El Shamieh S, Boulanger-Scemama E, Lancelot ME, Antonio A, Démontant V, Condroyer C, Letexier M, Saraiva JP, Mohand-Saïd S, Sahel JA, Audo I, Zeitz C - Biomed Res Int (2015)

Pedigrees of seven families with RP1 mutations underlying autosomal recessive rod-cone dystrophy. Affected and unaffected individuals are represented by shapes filled with black and white colors, respectively. Men and women are indicated by squares and circles, respectively. Index subjects are marked by ↖. Consanguinity is marked by a double horizontal line.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307388&req=5

fig3: Pedigrees of seven families with RP1 mutations underlying autosomal recessive rod-cone dystrophy. Affected and unaffected individuals are represented by shapes filled with black and white colors, respectively. Men and women are indicated by squares and circles, respectively. Index subjects are marked by ↖. Consanguinity is marked by a double horizontal line.
Mentions: Patient family F303: II.1 (CIC00445) was found to carry compound heterozygous variants: a nonsense mutation c.1625C>G, leading to a predicted premature stop (p.Ser542*) and a deletion c.4587_4590delTAAG leading to a frameshift and a premature termination codon (p.Ser1529Argfs*9) (Table 2, Figure 3). Patient family F752: II.1 (CIC01245) was also found to carry compound heterozygous variants: a 1 bp duplication c.2025dupA leading to p.Ser676Ilefs*22 and a 1 bp deletion c.2377delA leading to p.Arg793Glufs*55 (Table 2).

Bottom Line: Eight of the mutations were novel, and all cosegregated with severe arRCD phenotype, found associated with additional macular changes.Among the identified mutations, 4 belong to a region, previously associated with arRCD, and 5 others in a region previously associated with adRCD.These results point out for the necessity of sequencing RP1 when genetically investigating sporadic and arRCD.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U968, 75012 Paris, France ; Sorbonne Universités, UPMC University, Paris 06, UMR_S 968, Institut de la Vision, 75012 Paris, France ; CNRS, UMR_7210, 75012 Paris, France.

ABSTRACT
We report ophthalmic and genetic findings in families with autosomal recessive rod-cone dystrophy (arRCD) and RP1 mutations. Detailed ophthalmic examination was performed in 242 sporadic and arRCD subjects. Genomic DNA was investigated using our customized next generation sequencing panel targeting up to 123 genes implicated in inherited retinal disorders. Stringent filtering coupled with Sanger sequencing and followed by cosegregation analysis was performed to confirm biallelism and the implication of the most likely disease causing variants. Sequencing identified 9 RP1 mutations in 7 index cases. Eight of the mutations were novel, and all cosegregated with severe arRCD phenotype, found associated with additional macular changes. Among the identified mutations, 4 belong to a region, previously associated with arRCD, and 5 others in a region previously associated with adRCD. Our prevalence studies showed that RP1 mutations account for up to 2.5% of arRCD. These results point out for the necessity of sequencing RP1 when genetically investigating sporadic and arRCD. It further highlights the interest of unbiased sequencing technique, which allows investigating the implication of the same gene in different modes of inheritance. Finally, it reports that different regions of RP1 can also lead to arRCD.

Show MeSH
Related in: MedlinePlus