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- Abdulridha-Aboud, Wissam, et al.
(författare)
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Characterization of macular structure and function in two swedish families with genetically identified autosomal dominant retinitis pigmentosa
- 2016
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Ingår i: Molecular Vision. - 1090-0535. ; 22, s. 362-373
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To study the phenotype in two families with genetically identified autosomal dominant retinitis pigmentosa (adRP) focusing on macular structure and function. Methods: Clinical data were collected at the Department of Ophthalmology, Lund University, Sweden, for affected and unaffected family members from two pedigrees with adRP. Examinations included optical coherence tomography (OCT), full-field electroretinography (ffERG), and multifocal electroretinography (mfERG). Molecular genetic screening was performed for known mutations associated with adRP. Results: The mode of inheritance was autosomal dominant in both families. The members of the family with a mutation in the PRPF31 (p.IVS6+1G>T) gene had clinical features characteristic of RP, with severely reduced retinal rod and cone function. The degree of deterioration correlated well with increasing age. The mfERG showed only centrally preserved macular function that correlated well with retinal thinning on OCT. The family with a mutation in the RHO (p.R135W) gene had an extreme intrafamilial variability of the phenotype, with more severe disease in the younger generations. OCT showed pathology, but the degree of morphological changes was not correlated with age or with the mfERG results. The mother, with a de novo mutation in the RHO (p.R135W) gene, had a normal ffERG, and her retinal degeneration was detected merely with the reduced mfERG. Conclusions: These two families demonstrate the extreme inter-and intrafamilial variability in the clinical phenotype of adRP. This is the first Swedish report of the clinical phenotype associated with a mutation in the PRPF31 (p.IVS6+1G>T) gene. Our results indicate that methods for assessment of the central retinal structure and function may improve the detection and characterization of the RP phenotype.
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| 2. |
- Gorcenco, Sorina, et al.
(författare)
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Ataxia-pancytopenia syndrome with SAMD9L mutations
- 2017
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Ingår i: Neurology: Genetics. - 2376-7839. ; 3:5
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We describe the neurologic, neuroradiologic, and ophthalmologic phenotype of 1 Swedish and 1 Finnish family with autosomal dominant ataxia-pancytopenia (ATXPC) syndrome and SAMD9L mutations.METHODS: Members of these families with germline SAMD9L c.2956C>T, p.Arg986Cys, or c.2672T>C, p.Ile891Thr mutations underwent structured interviews and neurologic and ophthalmologic examinations. Neuroimaging was performed, and medical records were reviewed. Previous publications on SAMD9L-ATXPC were reviewed.RESULTS: Twelve individuals in both families were affected clinically. All mutation carriers examined had balance impairment, although severity was very variable. All but 1 had nystagmus, and all but 1 had pyramidal tract signs. Neurologic features were generally present from childhood on and progressed slowly. Two adult patients, who experienced increasing clumsiness, glare, and difficulties with gaze fixation, had paracentral retinal dysfunction verified by multifocal electroretinography. Brain MRI showed early, marked cerebellar atrophy in most carriers and variable cerebral periventricular white matter T2 hyperintensities. Two children were treated with hematopoietic stem cell transplantation for hematologic malignancies, and the neurologic symptoms of one of these worsened after treatment. Three affected individuals had attention deficit hyperactivity disorder or cognitive problems. Retinal dysfunction was not previously reported in individuals with ATXPC.CONCLUSIONS: The neurologic phenotype of this syndrome is defined by balance or gait impairment, nystagmus, hyperreflexia in the lower limbs and, frequently, marked cerebellar atrophy. Paracentral retinal dysfunction may contribute to glare, reading problems, and clumsiness. Timely diagnosis of ATXPC is important to address the risk for severe hemorrhage, infection, and hematologic malignancies inherent in this syndrome; regular hematologic follow-up might be beneficial.
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| 5. |
- Kjellström, Ulrika, et al.
(författare)
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Increased Plasma cGMP in a Family With Autosomal Recessive Retinitis Pigmentosa Due to Homozygous Mutations in the PDE6A Gene
- 2016
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 57:14, s. 6048-6057
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe genotype and phenotype in a family with autosomal recessive retinitis pigmentosa (arRP) carrying homozygous mutations in the gene for the α-subunit of cyclic guanosine monophosphate (cGMP)-hydrolyzing phosphodiesterase 6 (PDE6A). Moreover, to compare their plasma cGMP levels to controls, exploring the possible role for cGMP in RP diagnostics.Methods: Seven siblings and their parents were recruited. Microarray, verified by Sanger sequencing, was used for genotyping. Investigations included slit lamp and fundus examination, Goldmann perimetry, full-field and multifocal electroretinography (ERG), and optical coherence tomography (OCT). Cyclic GMP was measured with an immunoassay kit.Results: All siblings and their father were homozygous, and the mother heterozygous, for IVS6+1G>A in PDE6A. Seven family members also carried c1532G>A in ABCA4. Visual fields were constricted with mere central remnants in older subjects and additional temporal crescents in younger subjects. Visual acuity ranged from 0.8 to amaurosis. Full-field ERGs showed extinguished rod responses and minimal cone responses. Multifocal ERGs were severely reduced. Optical coherence tomography revealed either general attenuation or central macular edema. Mean plasma cGMP in patients was approximately twice that in controls.Conclusions: To our knowledge, this is the first phenotypic description of arRP due to homozygous IVS6+1G>A mutations in PDE6A and these seem here to be associated with severe RP leading to early extinction of rod responses as well as reduced macular function. Additionally, patients showed increased plasma levels of cGMP, indicating a possible role for cGMP measurements as part of the clinical tests for this and, after further investigations, maybe other forms of RP.
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| 6. |
- Kjellström, Ulrika
(författare)
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Reduced macular function in ABCA4 carriers.
- 2015
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Ingår i: Molecular Vision. - 1090-0535. ; 21, s. 767-782
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Tidskriftsartikel (refereegranskat)abstract
- To study retinal function and morphology in ABCA4 carriers to investigate if ABCA4 carriership is associated with any functional or morphological changes and, if so, to explore whether certain mutations may be associated with particularly severe alterations.
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| 7. |
- Lindmark, Ulrika, 1965-, et al.
(författare)
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The use of the concept of transition in different disciplines within health and social welfare: An integrative literature review
- 2019
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Ingår i: Nursing Open. - : John Wiley & Sons. - 2054-1058. ; 6:3, s. 664-675
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To continuing the quest of the concept of transition in nursing research and toexplore how the concept of transition is used in occupational therapy, oral health andsocial work as well as in interdisciplinary studies in health and welfare, between2003–2013.Design: An integrative literature review.Methods: PubMed, CINAHL, PsycINFO, DOSS, SocIndex, Social Science Citation Indexand AMED databases from 2003–2013 were used. Identification of 350 articles includingthe concept of transition in relation to disciplines included. Assessment of articlesare in accordance to Meleis’ typologies of transition by experts in each discipline.Chosen key factors were entered into Statistical Package for the Social Sciences (SPSS).Results: Meleis’ four typologies were found in all studied disciplines, except developmentin oral health. The health‐illness type was the most commonly explored,whereas in social work and in occupation therapy, situational transitions dominated.
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| 8. |
- Nikopoulos, Konstantinos, et al.
(författare)
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Mutations in CEP78 Cause Cone-Rod Dystrophy and Hearing Loss Associated with Primary-Cilia Defects
- 2016
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 99:3, s. 770-776
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Tidskriftsartikel (refereegranskat)abstract
- Cone-rod degeneration (CRD) belongs to the disease spectrum of retinal degenerations, a group of hereditary disorders characterized by an extreme clinical and genetic heterogeneity. It mainly differentiates from other retinal dystrophies, and in particular from the more frequent disease retinitis pigmentosa, because cone photoreceptors degenerate at a higher rate than rod photoreceptors, causing severe deficiency of central vision. After exome analysis of a cohort of individuals with CRD, we identified biallelic mutations in the orphan gene CEP78 in three subjects from two families: one from Greece and another from Sweden. The Greek subject, from the island of Crete, was homozygous for the c.499+1G>T (IVS3+1G>T) mutation in intron 3. The Swedish subjects, two siblings, were compound heterozygotes for the nearby mutation c.499+5G>A (IVS3+5G>A) and for the frameshift-causing variant c.633delC (p.Trp212Glyfs(∗)18). In addition to CRD, these three individuals had hearing loss or hearing deficit. Immunostaining highlighted the presence of CEP78 in the inner segments of retinal photoreceptors, predominantly of cones, and at the base of the primary cilium of fibroblasts. Interaction studies also showed that CEP78 binds to FAM161A, another ciliary protein associated with retinal degeneration. Finally, analysis of skin fibroblasts derived from affected individuals revealed abnormal ciliary morphology, as compared to that of control cells. Altogether, our data strongly suggest that mutations in CEP78 cause a previously undescribed clinical entity of a ciliary nature characterized by blindness and deafness but clearly distinct from Usher syndrome, a condition for which visual impairment is due to retinitis pigmentosa.
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| 9. |
- Schroeder, Marion, et al.
(författare)
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Full-field ERG as a predictor of the natural course of ABCA4-associated retinal degenerations
- 2018
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Ingår i: Molecular Vision. - 1090-0535. ; 24, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To assess retinal function in combination with the retinal structure in ABCA4-associated retinal degenerations. Moreover, to evaluate the possibility of predicting the natural course of these disorders. Methods: 34 patients with Stargardt disease or cone rod dystrophy carrying confirmed mutations in ABCA4 were selected from our retinitis pigmentosa (RP) register. Sequence analysis of the entire coding region of the ABCA4 gene was performed. The patients were subdivided into three groups based on their most recent visual fields. Group 1 included ten patients with central scotomas within 10°, group 2 included 19 patients with larger central scotomas of 10-35°, and group 3 included five patients with mere temporal residues. The patients underwent slit-lamp and fundus examinations, visual acuity testing, optical coherence tomography (OCT), fundus photography (color, red-free, and autofluorescence (AF) images), full-field electroretinography (ffERG), and multifocal electroretinography (mERG). FfERG and mERG results were analyzed statistically. Total rod and cone function, as well as macular function, was compared between the three groups and of each group to a normal material. In 23 patients who had undergone ffERG on a previous occasion, the 30 Hz flicker implicit time (IT) from the first visit was also analyzed. Results: The ffERG statistics revealed significant differences between the groups regarding cone and rod function with group 1 showing the highest amplitudes and the shortest ITs while group 3 demonstrated the lowest amplitudes and the most delayed ITs. When compared to controls, group 1 did not show any significant changes while groups 2 and 3 demonstrated reduced amplitudes and delayed 30 Hz ITs. Regarding estimation of the natural course, identical results of the 30 Hz IT were encountered for the groups also at the first visit early in the course of disease. Comparison of the mERGs showed significant differences with group 1 demonstrating the highest amplitudes and group 3 the lowest for all rings but rings 2 and 3 in the right eye for which the amplitudes were the second highest. The mERGs for each group were also compared to controls showing reduced mERG amplitudes for all rings in all groups, except group 1, left eye. OCT showed macular attenuation in all patients. Evaluation of the inner and outer photoreceptor junction (IS/OS) morphology revealed alterations related to macular function measured with mERG in all eyes. Eight patients in group 1 showed foveal IS/OS junction loss, one had foveal IS/OS junction disorganization, and one had IS/OS loss also beyond the fovea. In group 2, one patient had IS/OS junction loss confined to the fovea, and the rest showed total loss of IS/OS junctions. Group 3 was devoid of IS/OS junctions. Concerning the AF images, group 1 showed small areas of absent AF in the macula, peripapillary sparing, and flecks of increased and reduced AF in the posterior pole. In group 2, the central areas of absent AF were larger. Flecks of reduced AF were the most dominant and reached beyond the posterior pole. Seven of 19 patients had peripapillary sparing. In group 3, large confluent areas of reduced AF were found in the posterior pole and beyond with small areas of increased AF in the far periphery. No peripapillary sparing was seen. Conclusions: The current study demonstrates a significant difference in total retinal function, as well as macular function, between patients with ABCA4-associated retinal degeneration and a different degree of visual field defects with gradual deterioration of function along with increased visual field constriction. Likewise, the morphological changes, including the deviant AF pattern and loss of IS/OS junctions, that were related to macular function measured with mERG worsened with the degree of visual field defects. Moreover, in these groups of patients with ABCA4-associated retinal degenerations, full-field cone 30 Hz flicker IT seems to be a predictor of the natural course of the disease also on long-term follow-up.
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| 10. |
- Tracewska-Siemiątkowska, Anna, et al.
(författare)
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An Expanded Multi-Organ Disease Phenotype Associated with Mutations in YARS
- 2017
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Ingår i: Genes. - Basel, Switzerland : MDPI AG. - 2073-4425 .- 2073-4425. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- Whole exome sequence analysis was performed in a Swedish mother-father-affected proband trio with a phenotype characterized by progressive retinal degeneration with congenital nystagmus, profound congenital hearing impairment, primary amenorrhea, agenesis of the corpus callosum, and liver disease. A homozygous variant c.806T > C, p.(F269S) in the tyrosyl-tRNA synthetase gene (YARS) was the only identified candidate variant consistent with autosomal recessive inheritance. Mutations in YARS have previously been associated with both autosomal dominant Charcot-Marie-Tooth syndrome and a recently reported autosomal recessive multiorgan disease. Herein, we propose that mutations in YARS underlie another clinical phenotype adding a second variant of the disease, including retinitis pigmentosa and deafness, to the spectrum of YARS-associated disorders.
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