TULP1 mutation in two extended Dominican kindreds with autosomal recessive Retinitis pigmentosa

Banerjee, Poulabi; Kleyn, Patrick; Ja, Knowles; Ca, Lewis; Bm, Ross; Parano, Enrico; Sg, Kovats; Lee, John; Gk, Penchaszadeh; J, Ott; Jacobson, Samuel G.; Tc, Gilliam

doi:10.1038/ng0298-177

Cited by 130 publications

(67 citation statements)

References 12 publications

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“…This observation raises the question to know whether non-truncating mutations of this gene could be involved in autosomal recessive retinal dystrophies less severe than LCA. Indeed, LCA-associated mutations are commonly deleterious mutations and mutations in several LCA genes can be responsible for autosomal recessive retinal dystrophies (retinitis pigmentosa or cone-rod dystrophies) [Gu et al, 1997;Freund et al, 1997;Banerjee et al, 1998;Sohocki et al, 1998;Lewis et al, 1999;den Hollander 1999;Lorenz et al, 2000;den Hollander et al, 2001;Sohocki et al, 2001;Thompson et al, 2001Thompson et al, , 2002Hameed et al, 2003;den Hollander et al, 2004;Janecke et al, 2004;Perrault et al, 2004].…”

Section: Discussionmentioning

confidence: 99%

Mutations in LCA5 are an uncommon cause of Leber congenital amaurosis (LCA) type II

et al. 2007

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Leber congenital amaurosis (LCA) is the earliest and most severe form of inherited retinal dystrophy responsible for blindness or severe visual impairment at birth or within the first months of life. Up to date, ten LCA genes have been identified. Three of them account for ca. 43% of families and are responsible for a congenital severe stationary cone-rod dystrophy (Type I, 60 % of LCA) while the seven remaining genes account for 32% of patients and are responsible for a progressive yet severe rod-cone dystrophy (Type II, 40 % of LCA ). Recently, mutations in LCA5, encoding the ciliary protein lebercilin, were reported to be a rare cause of leber congenital amaurosis. The purpose of this study was to evaluate the involvement of this novel gene and to look for genotype-phenotype correlations. Here we report the identification of three novel LCA5 mutations (3/3 homozygous) in three families confirming the modest implication of this gene in our series (3/179; 1.7%). Besides, we suggest that the phenotype of these patients affected with a particularly severe form of LCA type II may represent a continuum with LCA type I.

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Section: Discussionmentioning

confidence: 99%

Mutations in LCA5 are an uncommon cause of Leber congenital amaurosis (LCA) type II

et al. 2007

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“…Today, 24 pathogenic variants have been described in TULP1, including 12 missense and 12 nonsense or frameshift mutations. [17][18][19][20][21][22][23][24][25][26][27] In all, 10 out of the 12 missense mutations are present in the tubby domain. The two novel missense mutations, R311Q and R342Q, that we have found in this study also affect amino acids of the tubby domain.…”

Section: Mutation Finding In Non-consanguineous Familiesmentioning

confidence: 99%

Combining gene mapping and phenotype assessment for fast mutation finding in non-consanguineous autosomal recessive retinitis pigmentosa families

et al. 2011

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Among inherited retinal dystrophies, autosomal recessive retinitis pigmentosa (arRP) is the most genetically heterogenous condition with 32 genes currently known that account for B60 % of patients. Molecular diagnosis thus requires the tedious systematic sequencing of 506 exons. To rapidly identify the causative mutations, we devised a strategy that combines gene mapping and phenotype assessment in small non-consanguineous families. Two unrelated sibships with arRP had whole-genome scan using SNP microchips. Chromosomal regions were selected by calculating a score based on SNP coverage and genotype identity of affected patients. Candidate genes from the regions with the highest scores were then selected based on phenotype concordance of affected patients with previously described phenotype for each candidate gene. For families RP127 and RP1459, 33 and 40 chromosomal regions showed possible linkage, respectively. By comparing the scores with the phenotypes, we ended with one best candidate gene for each family, namely tubby-like protein 1 (TULP1) and C2ORF71 for RP127 and RP1459, respectively. We found that RP127 patients were compound heterozygous for two novel TULP1 mutations, p.Arg311Gln and p.Arg342Gln, and that RP1459 patients were compound heterozygous for two novel C2ORF71 mutations, p.Leu777PhefsX34 and p.Leu777AsnfsX28. Phenotype assessment showed that TULP1 patients had severe early onset arRP and that C2ORF71 patients had a cone rod dystrophy type of arRP. Only two affected individuals in each sibship were sufficient to lead to mutation identification by screening the best candidate gene selected by a combination of gene mapping and phenotype characterization.

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“…Mutations in the human TULP1 gene are associated with retinitis pigmentosa (RP), an inherited form of progressive photoreceptor degeneration (Banerjee et al, 1998;Gu et al, 1998;Hagstrom et al, 1998;Paloma et al, 2000). RP patients with TULP1 mutations have a severe visual handicap in comparison with patients with RP due to defects in other genes.…”

Section: Introductionmentioning

confidence: 99%

Mutation screen of the TUB gene in patients with retinitis pigmentosa and Leber congenital amaurosis

Pauer

Traboulsi

et al. 2006

Experimental Eye Research

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TUB is the first identified member of the TULP family of four proteins with unknown function. A spontaneous mutation in murine tub causes retinal degeneration, obesity, and deafness. Mutations in another member of the TULP family, TULP1, are a cause of autosomal recessive retinitis pigmentosa (RP). These findings prompted us to investigate TUB as a candidate gene for RP and Leber congenital amaurosis (LCA). A mutation screen of the entire coding region of the TUB gene in 159 unrelated patients with autosomal recessive RP, 114 unrelated patients with simplex RP, and 21 unrelated patients with LCA uncovered 18 sequence variations. Of these, seven were missense mutations, six were isocoding changes, and five were intronic polymorphisms. All seven missense mutations were identified as heterozygous changes and no defect could be found in the other allele. None of the isocoding variants or intronic polymorphisms are predicted to create or destroy splice donor or acceptor sites based on splice-site prediction software. Although variant alleles of the TUB gene were found, none could be definitively associated with a specific retinal disease.

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TULP1 mutation in two extended Dominican kindreds with autosomal recessive Retinitis pigmentosa

Cited by 130 publications

References 12 publications

Mutations in LCA5 are an uncommon cause of Leber congenital amaurosis (LCA) type II

Mutations in LCA5 are an uncommon cause of Leber congenital amaurosis (LCA) type II

Combining gene mapping and phenotype assessment for fast mutation finding in non-consanguineous autosomal recessive retinitis pigmentosa families

Mutation screen of the TUB gene in patients with retinitis pigmentosa and Leber congenital amaurosis

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