Molecular Genetic Analysis of Two Functional Candidate Genes in the Autosomal Recessive Retinitis Pigmentosa, RP25, Locus

Annals of Human Genetics

et al. 2008

Retinitis pigmentosa (RP) is a group of retinal dystrophies characterised primarily by rod photoreceptor cell degeneration. Exhibiting great clinical and genetic heterogeneity, RP be inherited as an autosomal dominant (ad) and recessive (ar), X-linked (xl) and digenic disorder. RP25, a locus for arRP, was mapped to chromosome 6p12.1-q14.1 where several retinal dystrophy loci are located. A gene expressed in the retina, FAM46A, mapped within the RP25 locus, and computational data revealed its involvement in retinal signalling pathways. Therefore, we chose to perform molecular evaluation of this gene as a good candidate in arRP families linked to the RP25 interval. A comprehensive bioinformatic and retinal tissue expression characterisation of FAM46A was performed, together with mutation screening of seven RP25 families. Herein we present 4 novel sequence variants, of which one is a novel deletion within a low complexity region close to the initiation codon of FAM46A. Furthermore, we have characterised for the first time a coding tandem variation in the Caucasian population. This study reports on bioinformatic and moleculardata for the FAM46A gene that may give a wider insight into the putative function of this gene and its pathologic relevance to RP25 and other retinal diseases mapping within the 6q chromosomal interval.

Section: Discussionmentioning

confidence: 99%

“…Extensive genetic analysis of putative genes within the RP25 locus interval has led to the exclusion of a number of them as disease‐causing (Marcos et al 2000, 2002, 2003; Li et al 2001; Abd El‐Aziz et al 2005, 2006; Barragan et al 2005a; Barragan et al 2005b).…”

Section: Introductionmentioning

confidence: 99%

Genetic Analysis of FAM46A in Spanish Families with Autosomal Recessive Retinitis Pigmentosa: Characterisation of Novel VNTRs

Barragán

Borrego

Annals of Human Genetics

et al. 2008

“…The sequencing reaction was then performed as previously described 18. A direct sequence analysis of all probands was performed on the automated fluorescence DNA sequencer (ABI 3730, Applied Biosystems, Warrington), according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

Molecular genetic study of Egyptian patients with macular corneal dystrophy

El-Ashry

British Journal of Ophthalmology

Shalaby

et al. 2009

Aim: To identify the underlying genetic defect in Egyptian patients with macular corneal dystrophy (MCD). Methods:A clinical and molecular genetic study was performed on eleven patients from six families with MCD. Clinical diagnosis was confirmed by slit lamp biomicroscopy and histopathological examination of corneal buttons following keratoplasty. The coding region of the carbohydrate sulfotransferase (CHST6) gene was amplified by polymerase chain reaction (PCR) in all affected subjects. This was followed by direct sequencing and restriction digest analyses. Enzyme-linked immunosorbent assay (ELISA) of antigenic keratan sulfate (KS) in patients' serum was also performed.Results: Six homozygous mutations of which three are novel were identified within the coding region of CHST6 in six unrelated MCD families. The barely detectable level of antigenic KS in the serum of the affected individuals indicated that they all have MCD type I, including the subtype IA.Conclusions: This is the first report of molecular genetic analysis of MCD in the Egyptian population. Our data indicates the extensive allelic heterogeneity within CHST6 and further support its essential role in maintaining corneal transparency.3

“…Fifty‐four pairs of primers were designed using the Primer 3 Out put program (http://frodo.wi.mit.edu/cgibin/primer3/primer3_www.cgi), in order to screen the heterozygosity of the selected SNPs in all family members (primer information is available on request). Full PCR conditions and the sequencing protocol were as described previously (Abd El‐Aziz et al 2005).…”

Section: Methodsmentioning

confidence: 99%

A Novel Genetic Study of Chinese Families with Autosomal Recessive Retinitis Pigmentosa

Annals of Human Genetics

El-Ashry

Chan

et al. 2006

SummaryAutosomal recessive retinitis pigmentosa (arRP) is the commonest form of RP worldwide. To date 22 loci have been implicated in the pathogenesis of this disease; however none of these loci independently account for a significant proportion of recessive RP. Linkage studies of arRP in consanguineous families have been mainly based on homozygosity mapping, but this strategy cannot be applied in the case of non-consanguineous families. Therefore, we implemented a systematic approach for identifying the disease locus in three non-consanguineous Chinese families with arRP. Initially, linkage analysis using SNPs/microsatellite markers or mutation screening of known arRP genes excluded all loci/genes except RP25 on chromosome 6. Subsequently a whole genome scan for the three families using the 10K GeneChip Mapping Array was performed, in order to identify the possible disease locus. To the best of our knowledge this is the first report on the utilisation of the 10K GeneChip to study linkage in non-consanguineous Chinese arRP. This analysis indicates that the studied families are probably linked to the RP25 locus, a well defined arRP locus in other populations. The identification of another ethnic group linked to RP25 is highly suggestive that this represents a major locus for arRP.