PubMed Health⌕ Search

Biomedical subjects

P J Francis

Publications and source records attributed to P J Francis.

At least 19 recordsLinked to original sources
PubMed2005

Acute zonal occult outer retinopathy: towards a set of diagnostic criteria.

BACKGROUND: Individuals with acute zonal occult outer retinopathy (AZOOR) present with initially progressive scotomata and photopsia. Characteristically, the extent of the visual field defect is unexplained by fundal examination, but there is marked retinal dysfunction evident electrophysiologically. It is the authors' experience that a group of patients exhibit characteristic clinical and electrophysiological abnormalities, which serve as criteria for a working diagnosis. METHODS: A retrospective observational case series of 28 patients were identified with the clinical diagnosis of AZOOR who shared similar abnormal electrophysiology. Details of the history and ophthalmic findings were obtained from the case notes. RESULTS: Electrophysiology demonstrated a consistent pattern of dysfunction both at the photoreceptor/retinal pigment epithelial complex but also at inner retinal levels, essentially comprising a delayed 30 Hz flicker ERG and a reduction in the EOG light rise. CONCLUSION: This study determines diagnostic criteria applicable to a group of patients with AZOOR, typically those with classic symptomatology. Electrophysiological testing can help avoid lengthy, costly, and potentially invasive investigations, and the unnecessary use of immunosuppressive therapy.

Acute Disease↗
PubMed2005

Posterior polar cataract is the predominant consequence of a recurrent mutation in the PITX3 gene.

BACKGROUND: The authors recently identified three large genetically unrelated families with an identical 17 base pair duplication mutation in exon 4 of the PITX3 gene. Here, they report the detailed clinical phenotype. METHODS: Affected and unaffected individuals in the three families with autosomal dominant posterior polar cataract underwent full clinical examination and donated blood samples for DNA extraction and molecular genetic studies. RESULTS: In all three families, an identical 17 base pair duplication mutation in PITX3 was identified which co-segregated with disease status in the family. All affected individuals had bilateral progressive posterior polar cataracts. In one family, posterior polar cataract was the only clinical abnormality but in the other two families, one of 10 affected individuals and four of 11 affected individuals also had anterior segment mesenchymal dysgenesis (ASMD). CONCLUSION: Mutations in the PITX3 gene in humans result in posterior polar cataract and variable ASMD. The gene encodes a transcription factor which has a key role in lens and anterior segment development. The mechanism by which the mutant protein gives rise to such a regional pattern of lens opacity remains to be elucidated.

Adolescent↗
PubMed2005

Genetic and phenotypic heterogeneity in pattern dystrophy.

BACKGROUND: The pattern dystrophies (PD) represent a clinically heterogeneous family of inherited macular diseases frequently caused by mutations in the peripherin/RDS gene. Most previous studies have detailed the clinical findings in single families, making it difficult to derive data from which progression and visual outcome can be generalised. METHODS: Families were ascertained and clinically evaluated including angiography and electrophysiology where appropriate. RESULTS: In each of the six families with autosomal dominant PD, a mutation in the peripherin/RDS gene was identified, including a novel Cys250Phe variant. These data suggest that the condition is characterised by the accumulation of yellow to grey subretinal flecks, followed by pigmentary change accompanied by patches of chorioretinal atrophy. Subsequently, 50% (16/32) of individuals with PD developed poor central vision because of chorioretinal geographic atrophy or subretinal neovascularisation. The risk of these complications appears to increase with age. CONCLUSION: PD should not necessarily be considered a benign condition. Instead, patients should be counselled that there is a significant chance of losing central vision in their later years. Some elderly patients with probands showing PD may be misdiagnosed with age related macular degeneration owing to the phenotypic similarities between these conditions in the advanced state.

Adult↗
PubMed2003

A clinical and molecular genetic study of a rare dominantly inherited syndrome (MRCS) comprising of microcornea, rod-cone dystrophy, cataract, and posterior staphyloma.

AIM: To phenotype and genetically map the disease locus in a family presenting with autosomal dominant microcornea, rod-cone dystrophy, cataract, and posterior staphyloma. METHODS: Six affected and three unaffected members of the pedigree were examined. All individuals provided a history and underwent a full clinical examination with A-scan and B-scan ultrasonography and electrophysiological testing where appropriate. PCR based microsatellite marker genotyping using a positional candidate gene approach was then performed on DNA samples extracted from venous blood provided by each subject. RESULTS: The disorder is inherited as an autosomal dominant trait with variable expressivity and has a complex phenotype. Affected individuals had bilateral microcornea, pulverulent-like lens opacities, a rod-cone dystrophy and posterior staphyloma (MRCS). Using a positional candidate gene approach, the authors have evidence suggestive of linkage of this disorder to a region on 11q13 within the nanophthalmos 1 (NNO1) genetic interval. The small family size militates against achieving a LOD score of 3, but the haplotype data and the position of the putative MRCS locus within a known nanophthalmos locus are suggestive of linkage. A candidate gene within this region (ROM1) was screened and no mutations were found in affected members of the family. CONCLUSION: This rare developmental disorder has some phenotypic similarities to nanophthalmos and possibly maps to a locus within the genetic interval encompassing the NNO1 locus. Screening of candidate genes within this region continues.

Adolescent↗
PubMed2003

Genetic linkage analysis of a novel syndrome comprising North Carolina-like macular dystrophy and progressive sensorineural hearing loss.

AIM: To characterise the phenotype and identify the underlying genetic defect in a family with deafness segregating with a North Carolina-like macular dystrophy (NCMD). METHODS: Details of the family were obtained from the Moorfields Eye Hospital genetic clinic database and comprised eight affected, four unaffected members, and two spouses. Pedigree data were collated and leucocyte DNA extracted from venous blood. Positional candidate gene and genetic linkage strategies utilising polymerase chain reaction (PCR) based microsatellite marker genotyping were performed to identify the disease locus. RESULTS: The non-progressive ocular phenotype shared similarities with North Carolina macular dystrophy. Electro-oculography and full field electroretinography were normal. Progressive sensorineural deafness was also present in all affected individuals over the age of 20 years. Hearing was normal in all unaffected relatives. Haplotype analysis indicated that this family is unrelated to previously reported families with NCMD. Genotyping excluded linkage to the MCDR1 locus and suggested a potential novel disease locus on chromosome 14q (Z=2.92 at theta=0 for marker D14S261). CONCLUSION: The combination of anomalies segregating in this family represents a novel phenotype. This molecular analysis indicates the disease is genetically distinct from NCMD.

Adolescent↗
PubMed2002

A locus for isolated cataract on human Xp.

PURPOSE: To genetically map the gene causing isolated X linked cataract in a large European pedigree. METHODS: Using the patient registers at Birmingham Women's Hospital, UK, we identified and examined 23 members of a four generation family with nuclear cataract. Four of six affected males also had complex congenital heart disease. Pedigree data were collated and leucocyte DNA extracted from venous blood. Linkage analysis by PCR based microsatellite marker genotyping was used to identify the disease locus and mutations within candidate genes screened by direct sequencing. RESULTS: The disease locus was genetically refined to chromosome Xp22, within a 3 cM linkage interval flanked by markers DXS9902 and DXS999 (Zmax=3.64 at theta=0 for marker DXS8036). CONCLUSIONS: This is the first report of a locus for isolated inherited cataract on the X chromosome. The disease interval lies within the Nance-Horan locus suggesting allelic heterogeneity. The apparent association with congenital cardiac anomalies suggests a possible new oculocardiac syndrome.

Adolescent↗
PubMed2001

Visual outcome in patients with isolated autosomal dominant congenital cataract.

OBJECTIVE: To determine the visual outcome and surgical complication rates of patients with isolated inherited congenital cataract. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Patients and their families were ascertained from the genetic eye clinic and outpatient databases of Moorfields Eye Hospital, London, and invited to participate in the study. Four hundred twenty-two individuals from 72 pedigrees with this form of autosomal dominant cataract underwent ophthalmologic assessment. MAIN OUTCOME MEASURES: Visual acuity and surgical complications (glaucoma, retinal detachment, amblyopia). RESULTS: In this study 49.4% of patients (46.8% of those operated) achieved a visual acuity (VA) of 20/40 or better, 35.9% (36.1% of those operated) a VA between 20/50 and 20/200, and 14.7% (17.1% of those operated) worse than 20/200. Opacities that were more diffuse or did not lie close to the visual axis were associated with a better prognosis for vision; 6.6% had glaucoma and 5.0% had retinal detachment develop. CONCLUSIONS: Patients with isolated inherited congenital cataract have a better visual and surgical outcome than those with coexisting ocular and systemic abnormalities. The improved prognosis is related in part to the lack of other developmental abnormalities of the eye, and, because inherited cataracts are often partial at birth, surgery may be delayed to later infancy and childhood when there is a lower incidence of surgical complications and refractive correction is easier. Certain inherited phenotypes (lamellar, pulverulent, polymorphic, coralliform, and cortical) also seem to have a better prognosis, and this should be borne in mind when counseling these families. A large number of the patients in this study underwent surgery many years previously, when surgical outcomes were less favorable, and thus the results of this study establish only a minimum acuity dataset for the purposes of counseling.

Adolescent↗
PubMed2001

College Students' Perceptions of the C-Print Speech-to-Text Transcription System.

C-Print is a real-time speech-to-text transcription system used as a support service with deaf students in mainstreamed classes. Questionnaires were administered to 36 college students in 32 courses in which the C-Print system was used in addition to interpreting and note taking. Twenty-two of these students were also interviewed. Questionnaire items included student ratings of lecture comprehension. Student ratings indicated good comprehension with C-Print, and the mean rating was significantly higher than that for understanding of the interpreter. Students also rated the hard copy printout provided by C-Print as helpful, and they reported that they used these notes more frequently than the handwritten notes from a paid student note taker. Interview results were consistent with those for the questionnaire. Questionnaire and interview responses regarding use of C-Print as the only support service indicated that this arrangement would be acceptable to many students, but not to others. Communication characteristics were related to responses to the questionnaire. Students who were relatively proficient in reading and writing English, and in speech-reading, responded more favorably to C-Print.

Journal Article↗
PubMed2001

A novel keratocan mutation causing autosomal recessive cornea plana.

PURPOSE: Mutations in keratocan (KERA), a small leucine-rich proteoglycan, have recently been shown to be responsible for cases of autosomal recessive cornea plana (CNA2). A consanguineous pedigree in which cornea plana cosegregated with microphthalmia was investigated by linkage analysis and direct sequencing. METHODS: Linkage was sought to polymorphic microsatellite markers distributed around the CNA2 and microphthalmia loci (arCMIC, adCMIC, NNO1, and CHX10) using PCR and nondenaturing polyacrylamide gel electrophoresis before KERA was directly sequenced for mutations. RESULTS: Positive lod scores were obtained with markers encompassing the CNA2 locus, the maximum two-point lod scores of 2.18 at recombination fraction theta = 0 was obtained with markers D12S95 and D12S327. Mutation screening of KERA revealed a novel single-nucleotide substitution at codon 215, which results in the substitution of lysine for threonine at the start of a highly conserved leucine-rich repeat motif. Structural modeling predicts that the motifs are stacked into an arched beta-sheet array and that the effect of the mutation is to alter the length and position of one of these motifs. CONCLUSIONS: This report describes a novel mutation in KERA that alters a highly conserved motif and is predicted to affect the tertiary structure of the molecule. Normal corneal function is dependent on the regular spacing of collagen fibrils, and the predicted alteration of the tertiary structure of KERA is the probable mechanism of the cornea plana phenotype.

Child↗
PubMed2000

The genetics of childhood cataract.

Human congenital cataract has a diverse aetiology. In the proportion of cases where the cause is genetic, the disease shows wide phenotypic and genetic heterogeneity. Over the past few years, much research has been devoted to mapping the genes that underlie the disorder. This has been helped by the extensive array of naturally occurring and genetically engineered mouse cataract models and the abundance of human candidate genes. Most progress to date has been in the identification of genetic mutations causing autosomal dominant congenital cataract where eight genes have been implicated in cataractogenesis. Overall there is good correlation between the genetic mutations so far identified and the resulting lens phenotype but it is clear that mutations at more that one locus may give rise to similar forms of cataract. The identification of genes causing inherited forms of cataract will improve our understanding of the mechanisms underlying cataractogenesis in childhood and provide further insights into normal lens development and physiology. Perhaps more importantly, it is likely that some of the genes causing early onset cataract will be implicated in age related cataract which remains the commonest cause of blindness in the world.

Animals↗
PubMed1999

Lens biology: development and human cataractogenesis.

Cataract, or opacification of the lens of the eye, is the commonest cause of visual impairment world-wide. It is only treatable at present by surgical removal. Recent advances in our understanding of the genetics of human cataract, in particular the inherited congenital form, together with the development of an array of animal models have provided valuable new insights into normal vertebrate lens biology and the mechanisms that underlie cataract formation. In this article, we review the current state of research in these areas and discuss thinking regarding the relationship between the phenotypes observed and the underlying genotype in inherited cataract.

Animals↗
PubMed1999

The lens.

Explore the source record for details and available documents.

Cataract↗
PubMed1997

Post-operative iris prolapse following phacoemulsification and extracapsular cataract surgery.

PURPOSE: This study retrospectively compared and contrasted iris prolapse occurring following extracapsular cataract extraction and phacoemulsification. METHODS: The clinical notes of all patients who had undergone iris prolapse repair in the last 5 years at Southampton Eye Unit were recalled. Sixty-five patients (mean age 73 years; 41.6% male, 58.4% female) were identified out of a total of 7252 cataract operations performed (5983 extracapsular, 1269 phacoemulsification). RESULTS: Fifty-nine (93.3%) iris prolapses occurred following extracapsular surgery (83% had corneal incisions, 17% limbal). We identified 3 cases of phaco-related prolapse each of which occurred where the scleral tunnel had been extended to enable insertion of a 7.0 mm optic intraocular lens but had not been sutured. Overall, the average best corrected visual acuity achieved was 6/9. CONCLUSION: The authors conclude that although iris prolapse is much less common following phacoemulsification, all scleral sections that are extended should be sutured.

Aged↗