SEARCH · PubMed Health

Results for “Codon, Terminator”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources

PubMed1998

Molecular cloning of sucrase-isomaltase cDNA in the house musk shrew Suncus murinus and identification of a mutation responsible for isolated sucrase deficiency.

Isolated sucrase deficiency has been demonstrated in a line of house musk shrew, Suncus murinus (laboratory name: suncus). This animal belongs to the order Insectivore and is phylogenetically different from ordinarily used laboratory animals. They are believed to have evolved with mainly animal food without sucrose. To study the molecular basis of the sucrase deficiency in suncus, we cloned 6. 0-kilobase (kb) sucrase-isomaltase (SI, EC 3.2.1.48-10) cDNA from suncus intestinal cDNA library. The cDNA clone contained a 5442-base pair (bp)-long open reading frame preceded by an in frame termination codon. The deduced 1813-amino acid sequence showed 68.6, 71.2, and 74.7% similarity with those of rat, rabbit, and human, respectively. A cleavage site between isomaltase and sucrase as well as the region surrounding the catalytic sites for sucrase and isomaltase were conserved among the species. Out of 18 potential N-linked glycosylation sites, 5 were common among all 4 species. In the connecting segment which was enriched with O-linked glycosylation sites in the other species, only two sites were present in suncus. Northern blot analysis revealed that the 6.0-kb SI mRNA was expressed in the KAT line with intact sucrase-isomaltase activity. In contrast, 3.0-kb SI mRNA was expressed in suncus of the MI line with isolated sucrase deficiency. The 3.0-kb mRNA cosegregated with sucrase deficiency phenotype as an autosomal recessive trait. Sequence analysis revealed a 2-nucleotide deletion at position 2767-2768, which results in a frameshift and an immature termination codon. The cDNA of the MI line diverged from that of the KAT line at position 2865, having an 18-bp unique sequence followed by a poly(A) tail. The mutant cDNA encodes 922 amino acid residues which preserves the region for isomaltase but lacks that for whole sucrase. While the cells transfected with the plasmids expressing SI in the KAT line showed both sucrase and isomaltase activity, the plasmids expressing MI line cDNA showed only isomaltase activity. Thus it was concluded that the mutation in the SI gene was responsible for isolated sucrase deficiency in the MI line.

Amino Acid Sequence↗

PubMed1999

Role of p16/MTS1, cyclin D1 and RB in primary oral cancer and oral cancer cell lines.

One of the most important components of G1 checkpoint is the retinoblastoma protein (pRB110). The activity of pRB is regulated by its phosphorylation, which is mediated by genes such as cyclin D1 and p16/MTS1. All three genes have been shown to be commonly altered in human malignancies. We have screened a panel of 26 oral squamous cell carcinomas (OSCC), nine premalignant and three normal oral tissue samples as well as eight established OSCC cell lines for mutations in the p16/MTS1 gene. The expression of p16/MTS1, cyclin D1 and pRB110 was also studied in the same panel. We have found p16/MTS1 gene alterations in 5/26 (19%) primary tumours and 6/8 (75%) cell lines. Two primary tumours and five OSCC cell lines had p16/MTS1 point mutations and another three primary and one OSCC cell line contained partial gene deletions. Six of seven p16/MTS1 point mutations resulted in termination codons and the remaining mutation caused a frameshift. Western blot analysis showed absence of p16/MTS1 expression in 18/26 (69%) OSCC, 7/9 (78%) premalignant lesions and 8/8 cell lines. One cell line, H314, contained a frameshift mutation possibly resulting in a truncated p16/MTS1 protein. pRB was detected in 14/25 (56%) of OSCC but only 11/14 (78%) of these contained all or some hypophosphorylated (active) pRB. In premalignant samples, 6/8 (75%) displayed pRB, and all three normal samples and eight cell lines analysed contained RB protein. p16/MTS1 protein was undetectable in 10/11 (91%) OSCCs with positive pRB. Overexpression of cyclin D1 was observed in 9/22 (41%) OSCC, 3/9 (33%) premalignant and 8/8 (100%) of OSCC cell lines. Our data suggest p16/MTS1 mutations and loss of expression to be very common in oral cancer cell lines and less frequent in primary OSCC tumours. A different pattern of p16/MTS1 mutations was observed in OSCC compared to other cancers with all the detected p16/MTS1 mutations resulting in premature termination codons or a frameshift. The RB protein was expressed in about half (44%) of OSCCs and its expression inversely correlated with p16/MTS1 expression. In conclusion, we show that abnormalities of the RB pathway are a common mechanism of oral carcinogenesis.

Carcinoma, Squamous Cell↗

PubMed1999

Altered growth characteristics of recombinant respiratory syncytial viruses which do not produce NS2 protein.

The second gene in the 3'-to-5' gene order in respiratory syncytial virus (RSV) encodes the nonstructural protein NS2, for which there is no assigned function. To study the function of NS2, we have used a recently developed reverse genetics system to ablate expression of NS2 in recombinant RSV. A full-length cDNA copy of the antigenome of RSV A2 strain under the control of a T7 promoter was modified by introduction of tandem termination codons within the NS2 open reading frame (NS2stop) or by deletion of the entire NS2 gene (DeltaNS2). The NS2 knockout antigenomic cDNAs were cotransfected with plasmids encoding the N, P, L, and M2-1 proteins of RSV, each controlled by the T7 promoter, into cells infected with a vaccinia virus recombinant expressing T7 RNA polymerase. Recombinant NS2stop and DeltaNS2 RSVs were recovered and characterized. Both types of NS2 knockout virus displayed pinpoint plaque morphology and grew more slowly than wild-type RSV. The expression of monocistronic mRNAs for the five genes examined (NS1, NS2, N, F, and L) was unchanged in cells infected with either type of NS2 knockout virus, except that no NS2 mRNA was detected with the DeltaNS2 virus. Synthesis of readthrough mRNAs was affected only for the DeltaNS2 virus, where the NS1-NS2, NS2-N, and NS1-NS2-N mRNAs were replaced with the predicted novel NS1-N mRNA. Upon passage, the NS2stop virus stock rapidly developed revertants which expressed NS2 protein and grew with similar plaque morphology and kinetics wild-type RSV. Sequence analysis confirmed that the termination codons had reverted to sense, albeit not the wild-type assignments, and provided evidence consistent with biased hypermutation. No revertants were recovered from recombinant DeltaNS2 RSV. These results show that the NS2 protein is not essential for RSV replication, although its presence greatly improves virus growth in cell culture. The attenuated phenotype of these mutant viruses, coupled with the expected genetic stability associated with gene deletions, suggests that the DeltaNS2 RSV is a candidate for vaccine development.

Animals↗

PubMed1997

Nucleotide sequence of the gene encoding cis-biphenyl dihydrodiol dehydrogenase (bphB) and the expression of an active recombinant His-tagged bphB gene product from a PCB degrading bacterium, Pseudomonas putida OU83.

The nucleotide sequence of the bphB gene of Pseudomonas putida strain OU83 was determined. The bphB gene, which encodes cis-biphenyl dihydrodiol dehydrogenase (BDDH), was composed of 834 base pairs with an ATG initiation codon and a TGA termination codon. It can encode a polypeptide of 28.91 kDa, containing 277 amino acids. Promoter-like and ribosome-binding sequences were identified upstream of the bphB gene. The bphB nucleotide sequence was used to produce His-tagged BDDH, in Escherichia coli. The His-tagged BDDH construction, carrying a single 6 x His tail on the N-terminal portion, was active. The molecular mass of the native enzyme was 128 kDa and on SDS-PAGE analysis the molecular mass was 31 kDa. This enzyme requires NAD+ for its activity and its optimum pH is 8.5. Nucleotide and the deduced amino acid sequence analyses revealed a high degree of homology between the bphB gene from Pseudomonas putida OU83 and the bphB genes from P. cepacia LB400 and P. pseudoalcaligenes KF707.

Amino Acid Sequence↗

PubMed1988

High level expression and purification of HhaI methyltransferase.

A cloning system for the DNA-(cytosine-5)-methyltransferase MHhaI and high level expression of the enzyme are described. A parent plasmid was constructed from fragments of the MHhaI gene and synthetic oligonucleotides. The construct permits introduction of various restriction sites for cloning at precise positions near the initiation codon, and beyond the termination codon. The entire MHhaI coding sequence was introduced as a 1042 b.p. NdeI-XbaI fragment into the vector pAR3040 which contains the T7 RNA polymerase promoter. The resultant plasmid pTNX3 (MHhaI-pAR3040) was introduced into McrB- E. coli strains HB101 and GM2929, and expression of MHhaI was induced by infection with the lambda phage CE6 carrying the T7 RNA polymerase gene. In induced cells, catalytically active MHhaI was produced at a level that corresponds to about 8% of the total soluble protein; an insoluble form of the protein was also formed, but could be readily removed. The expressed soluble enzyme from HB101/pTNX3 was purified to apparent homogeneity in about 50% yield by a two-step chromatographic procedure involving DEAE-cellulose and Heparin-Sepharose; a one liter culture gave about 2.5 mg of pure enzyme. The molecular weight and kinetic properties of the expressed protein are identical to those reported for the authentic MHhaI, and its amino terminal sequence agrees with that predicted from the DNA sequence.

Cloning, Molecular↗

PubMed2006

Autoimmunity as a result of escape from RNA surveillance.

In previous studies, we detected a frame shift mutation in the gene encoding the autoantigen La of a patient with systemic lupus erythematosus. The mutant La mRNA contains a premature termination codon. mRNAs that prematurely terminate translation should be eliminated by RNA quality control mechanisms. As we find Abs specific for the mutant La form in approximately 30% of sera from anti-La-positive patients, we expected that mutant La mRNAs circumvent RNA control and the expression of mutant La protein could become harmful. Indeed, real-time PCR, immunostaining, and immunoblotting data of mice transgenic for the mutant La form show that mutant La mRNAs are not repressed in these animals and are translated to mutant La protein. In addition to the mutant La protein, we detected a minor portion of native human La in the mutant La-transgenic mice. Therefore, ribosomal frame shifting may allow the mutant La mRNA to escape from RNA control. Interestingly, expression of the mutant La mRNA results in a lupus-like disease in the experimental mice. Consequently, escape of mutant La mRNA from RNA control can have two effects: it 1) results in the expression of an immunogenic (neo)epitope, and 2) predisposes to autoimmunity.

3T3 Cells↗

PubMed1983

Tupaia (tree shrew) adenovirus DNA: sequence of the left-hand fragment corresponding to the transforming early region of human adenoviruses.

The nucleotide sequence of the left-hand region of the adenovirus DNA of the phylogenetically interesting tree shrew, (Tupaia belangeri) has been determined. Transcription signals, initiation codons, splice sites and termination codons were assigned on the basis of its relatedness to the EIA region of human adenoviruses 5, 7 and 12. A consensus sequence for encapsidation of adenoviral DNA that is based on the established packaging region of adenovirus 16 is proposed. The sequenced region includes the gene for a 18 000 dalton polypeptide that corresponds to the EIA proteins of the transforming region of the human serotypes. The deduced amino acid sequence of the 18 000 dalton TAV polypeptide contains a highly conserved central domain that is homologous to the middle of the 30 000 dalton polypeptides of human adenovirus indicating the significance of the central amino acid residues for the biological function of the EIA proteins.

Adenoviridae↗

PubMed1996

Structure of the pcbC gene encoding 2,3-dihydroxybiphenyl dioxygenase of Pseudomonas sp. P20.

Pseudomonas sp. P20 is a soil bacterium growing in biphenyl or 4-chlorobiphenyl as the sole carbon and energy source, where the initial catabolism of biphenyl to form benzoate is catalyzed by four enzymes encoded in the pcbABCD gene cluster. The nucleotide sequence of the 2,3-dihydroxybiphenyl dioxygenase gene corresponding to the pcbC gene was determined. The pcbC gene was composed of 921 base pairs with an ATG initiation codon and a TGA termination codon, which can encode a polypeptide of molecular mass 34 kDa containing 306 amino acids. A promoter-like sequence and ribosome-binding sequence were identified upstream of the initiation codon. The deduced amino acid sequence of 2,3-dihydroxybiphenyl dioxygenase exhibited 47% identity with that of corresponding enzyme of Pseudomonas sp. DJ-12, and less than 35% identity with those of other extradiol-type dioxygenases.

Amino Acid Sequence↗

PubMed1997

Structure of catechol 2,3-dioxygenase gene encoded in TOM plasmid of Pseudomonas cepacia G4.

The catechol 2,3-dioxygenase is an extradiol-type dioxygenase which cleaves the C-C bond at the meta position of catechol to form 2-hydroxymuconic semialdehyde. A catechol 2,3-dioxygenase gene (tomB) in the TOM plasmid of P. cepacia G4 has been cloned and its nucleotide sequence was analyzed. The enzyme gene consisted of 945 base pairs with an ATG initiation codon and a TGA termination codon which can encode a polypeptide of molecular weight 35 kDa containing 314 amino acid residues, and a putative ribosome-binding sequence was identified at approximately 10 nucleotides upstream of the initiation codon. The deduced amino acid sequence of catechol 2,3-dioxygenase from P. cepacia G4 exhibited 79-82% homologies with those of 3-methylcatechol 2,3-dioxygenase of P. putida UCC2 and catechol 2,3-dioxygenase of P. pickettii PKO1.

Amino Acid Sequence↗

PubMed1990

The virB operon of Agrobacterium tumefaciens pTiC58 encodes 11 open reading frames.

Agrobacterium tumefaciens genetically transforms plant cells by transferring a copy of its T-DNA to the plant where it is integrated and stably maintained. In the presence of wounded plant cells this process is activated and mediated by the products of the vir genes which are grouped into six distinct loci. The largest is the virB locus spanning 9.5 kb. Transposon mutagenesis studies have shown that virB gene products are required for virulence but their functions remain largely unknown. To provide information relevant to understanding the function of VirB polypeptides, the nucleotide sequence of the virB operon from a nopaline plasmid, pTiC58, is presented here. Eleven open reading frames (ORFs) are predicted from this sequence. The predicted sizes of 10 of the 11 VirB polypeptides are verified by specific expression in Escherichia coli. Only the product of the smallest ORF potentially encoding a 5.8 kDa polypeptide has not been detected. The initiation of translation of five virB ORFs occurs at codons that overlap the termination codons of the ORF immediately upstream; thus, translational coupling may be an important mechanism for efficient translation of the large virB polycistronic mRNA. Based on hydropathy plot analysis nine of the virB ORFs encode proteins that may interact with membranes; these data support the earlier hypothesis that virB gene products may form a membrane pore or channel to mediate exit of the T-DNA copy (T-strands) from Agrobacterium into the plant cell. A comparison of the two published octopine virB sequences with the nopaline sequence presented here is made.

Amino Acid Sequence↗

PubMed1986

Isolation, characterization and physiological properties of an autolytic-deficient mutant of Streptococcus pneumoniae.

A spontaneous mutation in the gene lyt encoding the pneumococcal autolysin has been characterized. This mutation, named lyt-32, which behaves as a high-efficiency marker in pneumococcal transformation, is a single base pair GC deletion causing the appearance of two consecutive termination codons in the amino terminal part of the sequence of the autolysin gene. The mutant lyt gene did not code for a polypeptide of relative molecular mass corresponding to the pneumococcal E form amidase in Escherichia coli maxicells. Pneumococcal cells containing the lyt-32 mutation (M32) were fully transformable, multiplied at a normal growth rate forming small chains and showed a tolerant response when treated with beta-lactam antibiotics. Strain M32 represents the first example of a mutant of Streptococcus pneumoniae completely lacking amidase as a consequence of an alteration in the structural gene coding for the pneumococcal autolysin.

Base Sequence↗

PubMed2004

New methods for detecting positive selection at single amino acid sites.

Inferring positive selection at single amino acid sites is of particular importance for studying evolutionary mechanisms of a protein. For this purpose, Suzuki and Gojobori (1999) developed a method (SG method) for comparing the rates of synonymous and nonsynonymous substitutions at each codon site in a protein-coding nucleotide sequence, using ancestral codons at interior nodes of the phylogenetic tree as inferred by the maximum parsimony method. In the SG method, however, selective neutrality of nucleotide substitutions cannot be tested at codon sites, where only termination codons are inferred at any interior node or the number of equally parsimonious inferences of ancestral codons at all interior nodes exceeds 10,000. Here I present a modified SG method which is free from these problems. Specifically, I use the distance-based Bayesian method for inferring the single most likely ancestral codon from 61 sense codons at each interior node. In the computer simulation and real data analysis, the modified SG method showed a higher overall efficiency of detecting positive selection than the original SG method, particularly at highly polymorphic codon sites. These results indicate that the modified SG method is useful for inferring positive selection at codon sites where neutrality cannot be tested by the original SG method. I also discuss that the p-distance is preferable to the number of synonymous substitutions for inferring the phylogenetic tree in the SG method, and present a maximum likelihood method for detecting positive selection at single amino acid sites, which produced reasonable results in the real data analysis.

Amino Acids↗

PubMed1982

Organization of the rat gamma-fibrinogen gene: alternative mRNA splice patterns produce the gamma A and gamma B (gamma ') chains of fibrinogen.

In a variety of species, including rodents and man, the gamma chain of fibrinogen consists of two nonallelic forms, called gamma A and gamma B, or gamma and gamma '. We have found that these two fibrinogen gamma chains in the rat arise by translation of two mRNAs of 1700 and 2200 nucleotides, which are produced from a single gene by alternative splice patterns. The more abundant, gamma A chain mRNA is 1561 nucleotides long, excluding the polyadenylated region, and encodes a protein 83% homologous with the human gamma A chain. A hydrophobic "signal" polypeptide of 25 amino acids is present at the amino terminus. The gamma B (gamma ') mRNA is identical with the gamma A sequence with the exception of a 513 bp insert located 202 bp from the poly(A) extension. This 513 bp insert is identical to the seventh and final intron of the gamma-fibrinogen gene, and is located four codons prior to the termination codon for the gamma A chain. Translation into this sequence produces a unique 12 amino acid carboxylterminus in the rat gamma B (gamma ') polypeptide that is homologous with the known carboxylterminus of the human gamma B (gamma ') chain.

Amino Acid Sequence↗

PubMed1995

Autoregulatory frameshifting in decoding mammalian ornithine decarboxylase antizyme.

Rat antizyme gene expression requires programmed, ribosomal frameshifting. A novel autoregulatory mechanism enables modulation of frameshifting according to the cellular concentration of polyamines. Antizyme binds to, and destabilizes, ornithine decarboxylase, a key enzyme in polyamine synthesis. Rapid degradation ensues, thus completing a regulatory circuit. In vitro experiments with a fusion construct using reticulocyte lysates demonstrate polyamine-dependent expression with a frameshift efficiency of 19% at the optimal concentration of spermidine. The frameshift is +1 and occurs at the codon just preceding the terminator of the initiating frame. Both the termination codon of the initiating frame and a pseudoknot downstream in the mRNA have a stimulatory effect. The shift site sequence, UCC-UGA-U, is not similar to other known frameshift sites. The mechanism does not seem to involve re-pairing of peptidyl-tRNA in the new frame but rather reading or occlusion of a fourth base.

Amino Acid Sequence↗

PubMed2005

Selenocysteine in proteins-properties and biotechnological use.

Selenocysteine (Sec), the 21st amino acid, exists naturally in all kingdoms of life as the defining entity of selenoproteins. Sec is a cysteine (Cys) residue analogue with a selenium-containing selenol group in place of the sulfur-containing thiol group in Cys. The selenium atom gives Sec quite different properties from Cys. The most obvious difference is the lower pK(a) of Sec, and Sec is also a stronger nucleophile than Cys. Proteins naturally containing Sec are often enzymes, employing the reactivity of the Sec residue during the catalytic cycle and therefore Sec is normally essential for their catalytic efficiencies. Other unique features of Sec, not shared by any of the other 20 common amino acids, derive from the atomic weight and chemical properties of selenium and the particular occurrence and properties of its stable and radioactive isotopes. Sec is, moreover, incorporated into proteins by an expansion of the genetic code as the translation of selenoproteins involves the decoding of a UGA codon, otherwise being a termination codon. In this review, we will describe the different unique properties of Sec and we will discuss the prerequisites for selenoprotein production as well as the possible use of Sec introduction into proteins for biotechnological applications. These include residue-specific radiolabeling with gamma or positron emitters, the use of Sec as a reactive handle for electophilic probes introducing fluorescence or other peptide conjugates, as the basis for affinity purification of recombinant proteins, the trapping of folding intermediates, improved phasing in X-ray crystallography, introduction of 77Se for NMR spectroscopy, or, finally, the analysis or tailoring of enzymatic reactions involving thiol or oxidoreductase (redox) selenolate chemistry.

Biotechnology↗

PubMed2004

The DNA beta satellite component associated with ageratum yellow vein disease encodes an essential pathogenicity protein (betaC1).

Ageratum yellow vein disease (AYVD) is caused by the geminivirus ageratum yellow vein virus (AYVV) and an associated DNA beta satellite. We have mapped a DNA beta transcript to a highly conserved open reading frame (betaC1 ORF). The most abundant transcript 5'-terminus is located 8 bases upstream of the betaC1 ORF putative initiation codon while the transcript terminates at multiple sites downstream from the putative termination codon. Disruption of betaC1 protein expression by the introduction of an internal nonsense codon prevented infection of the AYVV-satellite complex in ageratum and altered the phenotype in Nicotiana benthamiana to that produced by AYVV alone although the mutant was maintained in systemically infected tissues. Modification of the putative initiation codon to a nonsense codon produced an intermediate phenotype in N. benthamiana and a mild yellow vein phenotype in ageratum, suggesting that betaC1 protein expression could be initiated from an alternative site. N. benthamiana plants containing a dimeric DNA beta transgene produced severe developmental abnormalities, vein-greening, and cell proliferation in the vascular bundles. Expression of betaC1 protein from a potato virus X (PVX) vector also induced abnormal plant growth. Our results demonstrate that the satellite encodes at least one protein that plays a major role in symptom development and is essential for disease progression in ageratum, the natural host of the AYVD complex.

Ageratum↗

PubMed2006

Efficient expression of the 15-kDa form of infectious pancreatic necrosis virus VP5 by suppression of a UGA codon.

Infectious pancreatic necrosis virus (IPNV), a member of the Birnaviridae family, encodes a nonstructural VP5 protein from a small open reading frame (ORF), which overlaps with a major ORF encoding pVP2, VP4 and VP3 proteins. In majority of the Sp strains of IPNV sequenced to date, VP5 gene codes for a 15-kDa protein. However, we have shown that in highly virulent strains, there is a premature in-frame stop codon (UGA) at nucleotide (nt) position 427, (preceding the 15-kDa stop codon at nt position 511) which could encode a 12-kDa protein. Using reverse genetics, we recovered recombinant rNVI15, rNVI15-15K and rNVI15-DeltaVP5 viruses (which could encode 12 or 15-kDa VP5 or lack the expression of VP5, respectively) and demonstrated that VP5 is dispensable for viral replication in vivo but is not involved in virulence (Santi, N., Song, H., Vakharia, V. N., Evensen, Ø., 2005a. Infectious pancreatic necrosis virus VP5 is dispensable for virulence and persistence. J. Virol. 79, 9206-9216). Here, we utilized these viruses to investigate the gene expression of VP5 in vitro. Our results indicate that a 15-kDa VP5 is produced in rNVI15-infected cells, albeit at lower levels than in rNVI15-15K-infected cells, suggesting that the opal stop codon at nt 427 is suppressed. Furthermore, to examine translational suppression of the opal stop codon in VP5 gene, we constructed plasmids containing VP5-specific sequence and employed a yeast-based bicistronic dual-luciferase reporter system (Harger, J.W., Dinman, J.D., 2003. An in vivo dual-luciferase assay system for studying translational recoding in the yeast Saccharomyces cerevisiae. RNA 9, 1019-1024). Our results demonstrate that the VP5 sequence (with or without a stop codon) yielded approximately 13% termination suppression and the efficiency is directly related to the base immediately 3' of the termination codon, C>A>U>G.

Animals↗

PubMed2002

Radial perivascular retinal degeneration: a key to the clinical diagnosis of an ocular variant of Stickler syndrome with minimal or no systemic manifestations.

PURPOSE: To identify the genetic defect and present the ocular and extraocular findings in a large pedigree of predominantly ocular Stickler syndrome. DESIGN: Observational case series. METHODS: An eight-generation pedigree with hereditary retinal detachments was retrospectively and prospectively studied. Clinical information was obtained by medical records, telephone interviews, medical questionnaires, detailed ophthalmologic examinations, physical examinations, and personal observations. Linkage analysis of the COL2A1 gene was performed on 21 family members, and mutation analysis was performed on three family members. RESULTS: The pedigree consisted of 100 affected individuals. The ocular findings, frequently bilateral, consisted of radial perivascular retinal degeneration (RPRD) (100%), vitreous syneresis (100%), high myopia (76%), retinal detachment (65%), presenile cataract development (occurring before 50 years of age; 78%), and glaucoma (18%). Most (70%) of the retinal detachments occurred between 4 and 18 years of age. Extraocular manifestations, characteristic for Stickler syndrome, were detected in only four of 100 (4%) affected individuals. Linkage analysis with COL2A1 flanking markers showed evidence for linkage to the COL2A1 locus. The COL2A1 gene analysis identified a mutation converting a codon TGC for cysteine(86) to a premature termination codon in the alternatively spliced exon 2. CONCLUSIONS: A variant of Stickler syndrome, caused by mutations in exon 2 of COL2A1, may present in families with all of the ocular findings and no clinically identifiable extraocular findings associated with Stickler syndrome. The predominant ocular findings are a congenitally abnormal vitreous and an acquired radial perivascular retinal degeneration that may lead to complicated childhood and adult retinal detachment.

Adolescent↗