Melanie Sohocki Trapani

Labcorp · DNA Identification Testing Division

Leber congenital amaurosis (LCA) is the most severe inherited retinopathy, with the earliest age of onset. Because this currently incurable disease is present from birth and is a relatively rare disorder, the development of animal models that closely resemble the phenotype in patients is especially important. Our previous genetic analyses of LCA pa...

Mutations in AIPL1 are associated with Leber Congenital Amaurosis (LCA), a major cause of childhood blindness, yet the cellular function of the encoded protein has yet to be fully elucidated. In order to investigate the biochemistry of AIPL1, we have developed a system for the expression of the recombinant protein in bacteria and its subsequent pur...

To describe the phenotype of Leber congenital amaurosis (LCA) in 26 probands with mutations in aryl hydrocarbon receptor interacting protein-like 1 protein (AIPL1) and compare it with phenotypes of other LCA-related genes. To describe the electroretinogram (ERG) in heterozygote carriers. Patients with AIPL1-related LCA were identified in a cohort o...

Leber congenital amaurosis (LCA) is often considered the most severe inherited retinopathy, and AIPL1 was the fourth gene identified as associated with LCA. Although the function of AIPL1 is unknown, it has been reported to interact with NUB1. Here, we searched for a NUB1-binding site on AIPL1 and located it between amino acid residues 181 and 330...

Leber congenital amaurosis (LCA) is a genetically heterogeneous, autosomal recessive retinal degenerative disease responsible for approximately 5% of all inherited retinopathies (Kaplan et al., 1990). LCA is often considered the most severe form of childhood retinopathy, and infants with this disease are usually blind at birth. To date, mutations i...

Mutations in the aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) gene have been found in patients with Leber congenital amaurosis (LCA), a severe, early-onset form of retinal degeneration. To determine the normal function of AIPL1 and to better understand how mutations in this gene cause disease, we performed a yeast two-hybrid screen...

A Dutch family with autosomal dominant retinitis pigmentosa (adRP) displayed a phenotype characterized by an early age of onset, a diffuse loss of rod and cone sensitivity, and constricted visual fields (type I). One male showed a mild progression of the disease. Linkage analysis showed cosegregation of the genetic defect with markers from chromoso...

Leber's congenital amaurosis (LCA) represents the earliest and severest form of retinal dystrophy leading to congenital blindness. A total of 20% of children attending blind schools have this disease. LCA has a multigenic basis and is proving central to our understanding of the development of the retina. We describe the clinical and molecular genet...

Mutations in AIPL1 cause Leber congenital amaurosis (LCA), the most severe form of inherited blindness in children; however, the function of this protein in normal vision remains unknown. To determine amino acid subsequences likely to be important for function, we have compared the protein sequence of several species. Sequence conservation is highe...

To define the phenotypic expression of a deletion in the gene encoding the transcription factor CRX in a large, seven-generation, white family. Fourteen affected individuals, all heterozygous for the Leu146del12 mutation in the cone-rod homeobox gene (CRX), and four nonaffected relatives from the same family were examined with visual function tests...

Inherited retinopathies are a genetically and phenotypically heterogeneous group of diseases affecting approximately one in 2000 individuals worldwide. For the past 10 years, the Laboratory for Molecular Diagnosis of Inherited Eye Diseases (LMDIED) at the University of Texas-Houston Health Science Center has screened subjects ascertained in the Uni...

Leber congenital amaurosis (LCA, OMIM No. 204000) is a severe, early-onset inherited retinopathy that accounts for approximately 5% of all inherited retinal disease. To date, four genes associated with Leber congenital amaurosis have been identified, the most recent of which is the aryl-hydrocarbon interacting-like 1 gene, AIPL1 (OMIM No. 604392,60...

Inherited retinopathies are a genetically and phenotypically heterogeneous group of diseases affecting approximately one in 2000 individuals worldwide. For the past 10 years, the Laboratory for Molecular Diagnosis of Inherited Eye Diseases (LMDIED) at the University of Texas-Houston Health Science Center has screened subjects ascertained in the Uni...

Our aim was to describe the visual function characteristics of affected members from two unrelated families with different dominant mutations in the CRX gene. Standard full-field ERGs and high-intensity a-wave series were obtained. In addition, in most subjects, dark-adapted (DA) thresholds, color vision function (arrangement tests), and static per...

Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophy and the most frequent cause of inherited blindness in children. LCA is usually inherited in an autosomal recessive fashion, although rare dominant cases have been reported. One form of LCA, LCA4, maps to chromosome 17p13 and is genetically distinct from other fo...

Meeting Abstract: 1025B400

Leber congenital amaurosis (LCA, MIM 204000) accounts for at least 5% of all inherited retinal disease and is the most severe inherited retinopathy with the earliest age of onset. Individuals affected with LCA are diagnosed at birth or in the first few months of life with severely impaired vision or blindness, nystagmus and an abnormal or flat elec...

Retinitis pigmentosa is a genetically heterogeneous form of retinal degeneration that affects approximately 1 in 3500 people worldwide. Recently we identified the gene responsible for the RP1 form of autosomal dominant retinitis pigmentosa (adRP) at 8q11-12 and found two different nonsense mutations in three families previously mapped to 8q. The RP...

More than 100 genes causing inherited retinal diseases have been mapped to chromosomal locations, but less than half of these genes have been cloned. Mutations in many retina/pineal-specific genes are known to cause inherited retinal diseases. Examples include mutations in arrestin, rhodopsin kinase, and the cone-rod homeobox gene, CRX. To identify...

The goal of this study was to develop efficient methods to identify tissue-specific expressed sequence tags (ESTs) and to map their locations in the human genome. Through a combination of database analysis and laboratory investigation, unique retina-specific ESTs were identified and mapped as candidate genes for inherited retinal diseases. DNA sequ...

Mutations in the retinal-expressed gene CRX (cone-rod homeobox gene) have been associated with dominant cone-rod dystrophy and with de novo Leber congenital amaurosis. However, CRX is a transcription factor for several retinal genes, including the opsins and the gene for interphotoreceptor retinoid binding protein. Because loss of CRX function coul...

Two frequent protein variants of glutamate pyruvate transaminase (GPT) (E.C.2.6.1.2) have been used as genetic markers in humans for more than two decades, although chromosomal mapping of the GPT locus in the 1980s produced conflicting results. To resolve this conflict and develop useful DNA markers for this gene, we isolated and characterized cDNA...

The goal of our research is to determine the genes and mutations causing autosomal dominant retinitis pigmentosa (adRP) and related diseases. As is now common knowledge, this deceptively-simple goal is confounded by the exceptional heterogeneity of retinitis pigmentosa and other forms of retinal degeneration. This heterogeneity includes allelic het...

Bone morphogenetic proteins (BMPs) are multifunctional growth factors originally identified by their ability to induce ectopic bone formation. To investigate the function of one of the BMPs, BMP-7, we have generated BMP-7-deficient mice using embryonic stem cell technology. BMP-7-deficient mice die shortly after birth because of poor kidney develop...