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Kent W Small

Publications and source records attributed to Kent W Small.

11 recordsLinked to original sources
PubMed2006

No pathogenic mutations identified in the TGFBI gene in polymorphic corneal amyloid deposition.

PURPOSE: To determine whether primary, polymorphic, corneal amyloid deposition is associated with a mutation of the TGFBI gene. METHODS: Interventional case series of 8 patients. Slit lamp examination of all patients and photodocumentation of 5 patients were performed. Genomic DNA was isolated from buccal mucosal swabs obtained from all patients and all 17 exons of the TGFBI gene were amplified and sequenced. RESULTS: Multiple polymorphic, refractile deposits were noted throughout the central corneal stroma in all patients. The deposits appeared gray-white on direct illumination and translucent on retroillumination, characteristic of amyloid. In 2 patients, linear, branching opacities, reminiscent of lattice corneal dystrophy, were identified. Histopathologic examination confirmed the presence of stromal amyloid in the cornea of 1 patient who required corneal transplantation for pseudophakic corneal edema. Screening of the entire coding region of the TGFBI gene revealed 4 previously described synonymous substitutions, Leu217Leu, Val327Val, Leu472Leu, and Phe540Phe. A previously unreported missense change, Asp299Asn, was identified in one affected patient but not in her affected sister. No pathogenic mutations, including the Ala546Asp missense mutation previously associated with polymorphic corneal amyloidosis, were identified in any of the patients. CONCLUSIONS: TGFBI gene mutations were not identified in a series of patients with polymorphic corneal amyloid deposition. As bilateral, discrete stromal amyloid deposits may be dystrophic or degenerative, differentiation between these phenotypically similar conditions is facilitated with the use of molecular genetic analysis.

Aged↗
PubMed2005

Lattice dystrophy-like localized amyloidosis of the cornea secondary to trichiasis.

PURPOSE: To report a case of stellate and branching linear corneal stromal amyloid deposits secondary to trichiasis and the use of molecular genetic analysis to exclude lattice corneal dystrophy. METHODS: Case report and review of the literature. A 30-year-old man with a history of chronic ocular irritation was found to have distichiasis, epiblepharon, and unilateral corneal amyloidosis indistinguishable from lattice corneal dystrophy. Screening of the TGFBI gene was performed to rule out a previously reported mutation associated with lattice corneal dystrophy. RESULT: A corneal biopsy performed before presentation to the authors confirmed the presence of corneal amyloidosis. Screening of exons 4, 11, 12, and 14 in the TGFBI gene identified 2 previously reported polymorphisms, Leu472Leu and Phe540Phe, but no other coding region changes. CONCLUSION: Corneal stromal amyloidosis clinically resembling lattice corneal dystrophy may be associated with trichiasis. The exclusion of a TGFBI-associated corneal dystrophy in this case, leaving trichiasis as the most likely cause of the corneal amyloid deposition, demonstrates the utility of molecular genetic analysis in confirming or refuting a presumptive clinical diagnosis.

Adult↗
PubMed2005

Candidate gene screening for posterior polymorphous dystrophy.

PURPOSE: To perform candidate gene screening for posterior polymorphous corneal dystrophy (PPCD). The initial 3 genes chosen, ID1, BCL2L1, and VSX1, lie within the region on chromosome 20 to which the PPCD gene has been linked, and mutations in VSX1 have previously been identified in patients with PPCD. METHODS: DNA extraction, PCR amplification, and direct sequencing of the VSX1, BCL2L1, and ID1 genes were performed in 14 affected patients (12 families) as well as in unaffected family members and healthy control subjects. RESULTS: No coding region mutations in the BCL2L1 or ID1 genes were identified in affected patients. In the VSX1 gene, the previously identified Gly160Asp missense change was not present in any of our 12 probands, and the Asp144Glu mutation was identified in 1 affected patient as well as 1 unaffected control individual. Additionally, 2 synonymous substitutions were identified, Ala182Ala (8 affected patients from 8 families) and Gly239Gly (1 affected patient and 1 unaffected patient from the same family). In the ID1 gene, the synonymous substitution Gly216Gly was observed in 2 affected patients (2 families) who also demonstrated a single nucleotide change in both the 5'UTR (2129T>C) and 3'UTR (3267A>G). Another 5'UTR change, 2177T>C, was identified in 1 affected patient and his unaffected parent, both of whom also demonstrated the 2129T>C and 3267A>G changes. CONCLUSIONS: None of the 12 probands with PPCD demonstrated the previously described Gly160Asp mutation within the VSX1 gene. The Asp144Glu missense change, present in an affected patient as well as an unaffected control individual, appears to be a rare polymorphism, not a disease-causing mutation. No coding region changes were identified in the ID1 or BCL2L1 genes. Therefore, although we report a number of novel polymorphisms in the VSX1 and ID1 genes, the failure to identify any sequence variants that sort with the disease phenotype suggests that other genetic factors are involved in PPCD.

Corneal Dystrophies, Hereditary↗
PubMed2004

Macular hemorrhage after laser in situ keratomileusis (LASIK) with femtosecond laser flap creation.

PURPOSE: To report the first case of macular hemorrhage following laser in situ keratomileusis (LASIK) with femtosecond laser flap creation. DESIGN: Observational case report. METHODS: A 36-year-old woman underwent uncomplicated, bilateral, simultaneous LASIK procedures for correction of moderate myopia (-5.00 diopters OD and -6.00 diopters OS). LASIK flap creation was performed using the IntraLase femtosecond laser. RESULTS: On postoperative day 1, the patient's uncorrected and best-corrected visual acuities were 20/20 OD and 20/40 OS. A dilated fundoscopic examination revealed a one-third disk diameter macular hemorrhage OS. An intravenous fluorescein angoiogram ruled out the presence of predisposing macular pathology. Two months after LASIK, the macular hemorrhage had cleared, and 6 months later, the BCVA improved to 20/25 OS. CONCLUSIONS: Macular hemorrhage may occur after LASIK, even in the absence of previously identified risk factors, such as high myopia, pre-existing choroidal neovasculaization, lacquer cracks, and sudden changes in intraocular pressure associated with microkeratome-assisted flap creation.

Adult↗
PubMed2004

Lattice corneal dystrophy associated with the Ala546Asp and Pro551Gln missense changes in the TGFBI gene.

PURPOSE: To report a phenotypic variant of lattice corneal dystrophy associated with two missense changes, Ala546Asp and Pro551Gln, in the transforming growth factor-beta-induced gene (TGFBI). DESIGN: Experimental study. METHODS: Genomic DNA was obtained from the proband as well as affected and unaffected family members. Exons 4, 11, 12, and 14 of the TGFBI gene were amplified and sequenced. Additionally, a corneal button excised from the proband was examined by light and transmission electron microscopy. Haplotype analysis was performed on the proband's family and members of a previously identified pedigree with the same TGFBI gene missense changes. RESULTS: Bilateral, symmetric, radially arranged, branching refractile lines within and surrounding an area of central anterior stromal haze were noted in the proband. Multiple polymorphic, refractile deposits were noted in the mid and posterior stroma in both the proband and her daughter. Light and electron microscopic analyses demonstrated amyloid and excluded the presence of deposits characteristic of granular corneal dystrophy. Screening of TGFBI exon 12 in the proband and her affected daughter revealed two missense changes, Ala546Asp and Pro551Gln (both absent in 250 control chromosomes). Haplotype analysis suggested that the mutations in this family and in a previously identified pedigree reflect a founder effect, rather than an independent occurrence. CONCLUSIONS: We present a phenotypic variant of lattice corneal dystrophy associated with the Ala546Asp and Pro551Gln missense changes in exon 12 of the TGFBI gene. A common ancestor appears to account for the missense mutations observed in this pedigree and in a previously reported family.

Adult↗
PubMed2003

Identification of GUCY2D gene mutations in CORD5 families and evidence of incomplete penetrance.

Cone rod dystrophy 5 (CORD5) is an autosomal dominant retinal disease that primarily affects cone function. The locus has previously been mapped to human chromosome 17p12-p13 between the markers D17S926/D17S849 and D17S945/D17S804. One of our "unaffected" recombinant individual from family 1175 was subsequently found to cross through this interval. Reexamination revealed that he was in fact mildly affected. This expanded the minimum candidate region. Direct sequencing of the GUCY2D and other candidate genes within this interval was carried out on 2 American families affected with CORD5. There was an R838C missense mutation within the GUCY2D gene in one and a R838H missense mutation in another families. The previously reported mutations for CORD6 are clustered at the same position within the gene. These results indicate that both CORD5 (MIM# 600977) and CORD6 (MIM# 601777) are actually the same disease. We conclude that significant variability in expression and incomplete penetrance exists even within one family.

Adolescent↗
PubMed2003

Hereditary motor and sensory neuropathy type VI with optic atrophy.

PURPOSE: To present the detailed clinical findings of a large family with hereditary motor and sensory neuropathy type VI (HMSN VI), a syndrome featuring optic atrophy. DESIGN: Observational case series. METHODS: A detailed history was obtained and physical examination was made of the extended family of the proband for evidence of neurologic dysfunction. The OPA1 gene was screened for mutations by direct DNA sequencing. RESULTS: Twelve of 97 family members examined are affected with signs of HMSN VI. Three other members have either optic atrophy or peripheral neuropathy, thus allowing an appreciation of the full clinical spectrum of disease. No mutations were found in the OPA1 gene. CONCLUSIONS: This family demonstrates the variable expressivity of this disorder as well as incomplete penetrance. This is the largest known family with HMSN VI. No association was found with changes in the OPA1 gene.

Adult↗
PubMed2002

Alu DNA polymorphism in ACE gene is protective for age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. We report an association between an Alu polymorphism in the angiotensin-converting enzyme (ACE) gene with the dry/atrophic form of AMD. Using the polymerase chain reaction (PCR) on genomic DNA isolated from patients with AMD (n=173), and an age-matched control population (n=189), we amplified a region polymorphic for an Alu element insertion in the ACE gene. The Alu(+/+) genotype occurred 4.5 times more frequently in the control population than the dry/atrophic AMD patient population, (p=0.004). The predominance of the Alu(+/+) genotype within the unaffected control group represents a protective insertion with respect to the human ocular disease, dry/atrophic AMD. This is the first demonstration of an Alu element insertion exerting protective effects against a known human disease.

Age Factors↗
PubMedDate not supplied

Crystalline retinopathies.

Many types of crystalline retinopathies have been described, associated with a myriad of medical conditions ranging from chronic retinal conditions to inherited systemic diseases. This comprehensive review summarizes the different types of crystalline retinopathies, including their clinical presentations, diagnostic criteria, pathology, and treatment options.

Crystallization↗