Présentation de l'adaptation française de « l'échelle de coparentage » de McHale pour familles avec jeunes enfants [Presentation of the french adaptation of McHale's coparenting scale for families with young children.]

The aim of this paper is to present McHale's coparenting scale,a self-administered questionnaire enabling assessment of the quality of coparenting, and first steps in structural and construct validation of the French version. A total of 41 French speaking Swiss families and 84 US families completed this questionnaire and the Dyadic Adjustment Scale, a measure of marital satisfaction. The results of the Swiss families correspond to those of US families: first, items distributed into four factors (family integrity, conflict, affection and disparagement) and second, a partial link was found between quality of coparenting and marital adjustment. This finding supports the construct validity of the questionnaire, reflecting the established link between these two family sub-systems. Given that coparenting quality has a major influence on children's socio-affective development, the questionnaire will find great use in assessing not just negative features of coparenting, such as conflicts and disparagement, but also positive components such as warmth and support. This will be an important asset for research as well as clinical purposes.

Novel ADAM9 homozygous mutation in a consanguineous Egyptian family with severe cone-rod dystrophy and cataract.

OBJECTIVE: To genetically and phenotypically describe a new ADAM9 homozygous mutation in a consanguineous family from Egypt with autosomal recessive cone-rod dystrophy (arCRD), anterior polar and posterior subcapsular cataract. DESIGN, SETTING AND PARTICIPANTS: The parents and their six children were included. They underwent a complete ophthalmic examination with fundus photography and optical coherence tomography (OCT). INTERVENTION: DNA was extracted from peripheral blood from all family members. Screening for mutations in genes known to be implicated in retinal disorders was done with the IROme, an in-solution enrichment array, followed by high-throughput sequencing. Validation of the results was done by bidirectional Sanger sequencing of ADAM9 exon 14, including exon-intron junctions. Screening of normal controls was done by denaturing high-performance liquid chromatography. RESULTS: arCRD was diagnosed in the mother and two of her children. Bilateral anterior polar and posterior subcapsular cataract was observed in the mother and bilateral dot cataract was diagnosed in three of the four children not affected with arCRD, one of whom also had glaucoma. The characteristics of the arCRD were childhood-onset visual impairment, reorganisation of the retinal pigment epithelium with mid-periphery greyish-white discolouration, attenuated retinal vasculatur and optic disc pallor. A coloboma-like macular lesion was observed in one of the arCRD-affected children. IROme analysis identified a c.1396-2A>G homozygous mutation in the splice acceptor site of intron 13 of ADAM9. This mutation was homozygous in the two children affected by arCRD and in their affected mother. This mutation was heterozygous in the unaffected father and the four unaffected children. CONCLUSIONS AND RELEVANCE: We identified a novel autosomal recessive ADAM9 mutation causing arCRD in a consanguineous Egyptian family. The percentage of arCRD cases caused by mutation in ADAM9 remains to be determined. Few families are reported in the literature to date; hence extensive clinical descriptions of families with ADAM9 mutations are of significant importance.

Clinical and genetic investigation of a large Tunisian family with complete achromatopsia: identification of a new nonsense mutation in GNAT2 gene.

Complete achromatopsia is a rare autosomal recessive disease associated with CNGA3, CNGB3, GNAT2 and PDE6C mutations. This retinal disorder is characterized by complete loss of color discrimination due to the absence or alteration of the cones function. The purpose of the present study was the clinical and the genetic characterization of achromatopsia in a large consanguineous Tunisian family. Ophthalmic evaluation included a full clinical examination, color vision testing and electroretinography. Linkage analysis using microsatellite markers flanking CNGA3, CNGB3, GNAT2 and PDE6C genes was performed. Mutations were screened by direct sequencing. A total of 12 individuals were diagnosed with congenital complete achromatopsia. They are members of six nuclear consanguineous families belonging to the same large consanguineous family. Linkage analysis revealed linkage to GNAT2. Mutational screening of GNAT2 revealed three intronic variations c.119-69G>C, c.161+66A>T and c.875-31G>C that co-segregated with a novel mutation p.R313X. An identical GNAT2 haplotype segregating with this mutation was identified, indicating a founder mutation. All patients were homozygous for the p.R313X mutation. This is the first report of the clinical and genetic investigation of complete achromatopsia in North Africa and the largest family with recessive achromatopsia involving GNAT2; thus, providing a unique opportunity for genotype-phenotype correlation for this extremely rare condition.

Autofluorescence Findings Of A Novel Maculopathy In Patient With Spinocerebellar Ataxia Type 1 And Of A Cone - Rod Type Retinal Dysfunction In Three Generation Family With Spinocerebellar Ataxia Type 7

Purpose: To report a novel maculopathy in a patient with SCA1. To describe autofluorescence findings in family with SCA7 and associated cone-rod retinal dysfunction.Methods: 4 affected patients from two families were assessed to investigate a progressive loss of visual acuity (VA). Examinations included fundus photography, autofluorescence (AF) fundus fluorescein angiogragraphy (FFA) and optical coherence tomography. Electroretinogram (full-field) was performed in 2 affected patients. All patients had color vision testing using Ishihara pseudoisochromatic plates. Molecular analysis was performed in family 2.Results: The patient with known diagnosis of SCA1 had a visual acuity of 20/200 bilaterally and dyschromatopsia. He had saccadic pursuit. Fundus examination showed mild retinal pigment epithelium (RPE) changes at the macula. OCT showed bilateral macular serous detachment, which was not obvious at the FFA and explained his VA. AF imaging showed a central hyperfluorescence. The 45 year old proband from family 2 had a visual acuity of 200/20 and dyschromatopsia. ERG testing showed cone type dysfunction of photoreceptors. Her daughter affected at a younger age had the same ERGs findings. Fundus examination showed mild RPE changes in proband, normal findings in her daughter. AF imaging of both patients showed a ring of high density AF around the fovea. The ring was also obvious on near infrared AF. Later onset of gait imbalance led to the diagnosis of SCA7Conclusions: Within the group of spinocerebellar ataxias, only the type 7 is associated with retinal dysfunction. We present the first report of maculopathy associated with SCA1 causing severe vision loss. The ring of high density AF in SCA7 confirmed an early retinal photoreceptor dysfunction in patient with normal fundus.

Mutation in the gene for connexin 30.3 in a family with erythrokeratodermia variabilis.

Erythrokeratodermia variabilis (EKV) is an autosomal dominant keratinization disorder characterized by migratory erythematous lesions and fixed keratotic plaques. All families with EKV show mapping to chromosome 1p34-p35, and mutations in the gene for connexin 31 (Cx31) have been reported in some but not all families. We studied eight affected and three healthy subjects in an Israeli family, of Kurdish origin, with EKV. After having mapped the disorder to chromosome 1p34-p35, we found no mutations in the genes for Cx31, Cx31.1, and Cx37. Further investigation revealed a heterozygous T-->C transition leading to the missense mutation (F137L) in the human gene for Cx30.3 that colocalizes on chromosome 1p34-p35. This nucleotide change cosegregated with the disease and was not found in 200 alleles from normal individuals. This mutation concerns a highly conserved phenylalanine, in the third transmembrane region of the Cx30.3 molecule, known to be implicated in the wall formation of the gap-junction pore. Our results show that mutations in the gene for Cx30.3 can be causally involved in EKV and point to genetic heterogeneity of this disorder. Furthermore, we suggest that our family presents a new type of EKV because of the hitherto unreported association with erythema gyratum repens.

Variable phenotypic expressivity in a Swiss family with autosomal dominant retinitis pigmentosa due to mutation T494m in the Prpf3 gene

Purpose:to describe the clinical features in a five generations family segregating autosomal dominant retinitis pigmentosa and to identify the causative gene Patient and Methods:Twenty five individuals of a large five-generation family originating from Western Switzerland were ascertained for phenotypic and genotypic characterization. Ophthalmologic evaluations included color vision testing, Goldman perimetry and digital fundus photography. Some patients had autofluorescence (AF) imaging, ocular coherence tomography (OCT) and ISCEV-standard full-field electroretinography (ERG). Blood samples were collected from 10 affected (4 to 70 years of age) and 15 unaffected members after informed consent. DNA was isolated and exons and intron-exons junctions of known adRP genes were sequenced using a Big Dye sequencing kit 1.1. Results:Age of onset of nightblindness and severity of progression of the disease was variable between members of the family. Some patients had early onset of nightblindess aged 3, others at mid-twenties. Most patients had visual acuity above 0.6 for the first 4 decades. Two older patients still had good vision (0.4) in their seventies. Myopia (range: -2 to -5) was noticed in most affected subjects. Fundus findings showed areas of atrophy along the arcades. The AF imaging showed a large high density ring bilaterally. A T494M change was found in exon 11 of PRPF3 gene. The change segregates with the disease in the family. Conclusion: A mutation in the PRPF3 gene is rare compared with other genes causing ADRP. Although a T494M change has been reported, our family is the first one with a variable expressivity. Mutations in PRPF3 gene can cause a variable phenotype of ADRP unlike the previously described Danish and English families. Our report gives a better understanding as to the phenotype/genotype description of ADRP due to PRPF3 mutation.

Three Generation Family With Pattern Dystrophy and a Successful Treatment of Subfoveal Cnv Related to Pattern Dystrophy With Anti-vegf Intravitreal Injections

Purpose: To phenotype a large 3 generation Swiss family with pattern dystrophy and to report a successful result of treatment with ranibizumab of a subfoveal choroidal neovascularisation (CNV) associated with pattern dystrophy in 1 patient Patients and methods: 4 affected and 3 unaffected patients (3 female 4 male, age range: 19 - 80 years) were assessed with a complete ophthalmologic examination. AF images were taken using Heidelberg Retina Angiograph and the digital color photos, fluorescein angiogragraphy (FFA) using the same TOPCON 501 camera. Electroretinogram (full-field and multifocal) was performed in 1 affected patient. One 48 years old patient developed a subfoveal CNV, which was treated with 2 injections of ranibizumab, at 3 months interval. Blood sample was taken for molecular analysis (screening of the gene RDS). Results: Two patients had a typical fundoscopic appearance of pattern dystrophy with butterfly shaped deposit at the fovea and some peripheral flecks, as shown with AF imaging.. Two others affected patients had a more unusual appearance with some macular atrophy in one or both eyes, surrounded by flecks. The visual acuity ranged from 1.0 to 0.1 according to Snellen EDTRS chart. The patient with subfoveal CNV presented a drop of vision form 1.0 to 0.6 within 10 days prior to the diagnosis and also reported some metamorphopsia. FFA and optical computerized tomography (OCT) confirmed a classic CNV. After the 1st injection her vision improved to 1.0 but persistent metamorphopsia and fluid on OCT motivated a second injection. One month after the second injection the OCT was flat and the patient had no symptoms. The results of RDS screening will be presented at the meeting. Conclusion: We present a family with pattern dystrophy, with some members having an unusual fundus appearance, which was mistaken for an early onset dry AMD. The AF imaging is a useful tool in diagnosing this condition. A CNV associated with pattern dystrophy a rare. This is the first report of a successful treatment of the CNV with anti-VEGF intravitreal injections.

. Phenotype/genotype correlation associated with a novel nonsense Glu20stop mutation in the Rp2 gene in a three-generation family with x-linked retinitis pigmentosa

Purpose: To assess the phenotype of patients in a large 3 generation Swiss family with X-linked retinitis pigmentosa (XLRP) due to a novel nonsense mutation Glu20stop in RP2 gene and to correlate with the genotype. Methods: 6 affected patients (1 male, 5 females, age range: 23 - 73 years) were assessed with a complete ophthalmologic examination. All had fundus autofluorescence images, standardised electroretinography, Goldmann visual fields and Optical Coherence Tomography. In addition, medical records of 2 affected male patients were reviewed. Blood sample was taken for molecular analysis. Results: The male patients were severely affected at a young age with early macular involvement. The youngest 23 y old male had also high myopia and vision of less than 0.05 according to Snellen EDTRS chart bilaterally. All 5 female carriers had some degree of rod-cone dystrophy, but no macular involvement. The visual acuity was 1.0 in the younger carriers, while the 73 years old had VA of 0.5. Two females had mild myopia (range -0.75 to -2) and one had anisometropia of 3.5D, with the more severely affected eye being myopic. Three out of 5 female carriers had optic nerve drusen. Conclusions: We report a novel Glu20stop mutation in RP2 gene, which is a rare cause of XLRP. Our description of severe phenotype in male patients with high myopia and early macular atrophy confirms previous reports. Unlike previous reports, all our female carriers had RP, but not macular involvement or high myopia. The identifiable phenotype for RP2-XLRP aids in clinical diagnosis and targeted genetic screening.

Using group role-playing games with gifted children and adolescents: A psychosocial intervention model

Gifted children develop asynchronously, often advanced for their age cognitively, but at or between their chronological and mental ages socially and emotionally (Robinson, 2008). In order to help gifted children and adolescents develop and practice social and emotional self-regulation skills, we investigated the use of an Adlerian play therapy approach during pen-and-paper role-playing games. Additionally, we used Goffman's (1961, 1974) social role identification and distance to encourage participants to experiment with new identities. Herein, we propose a psychosocial model of interactions during role-playing games based on Goffman's theory and Adlerian play therapy techniques, and suggest that role-playing games are an effective way of intervening with gifted children and adolescents to improve their intra- and interpersonal skills. We specifically targeted intrapersonal skills of exercising creativity, becoming self-aware, and setting individual goals by raising participants' awareness of their privately logical reasons for making decisions and their levels of social interest. We also targeted their needs and means of seeking significance in the group to promote collaboration and interaction skills with other gifted peers through role analysis, embracement, and distancing. We report results from a case study and conclude that role-playing games deserve more attention, both from researchers and clinical practitioners, because they encourage change while improving young clients' social and emotional development.

Tau and neurofilaments in a family with frontotemporal dementia unlinked to chromosome 17q21-22.

A Swiss frontotemporal dementia (FTD) kindred with extrapyramidal-like features and without motor neuron disease shows a brain pathology with ubiquitin-positive but tau-negative inclusions. Tau and neurofilament modifications are now studied here in three recently deceased family members. No major and specific decrease of tau was observed as described by others in, e.g., sporadic cases of FTD with absence of tau-positive inclusions. However, a slight decrease of tau, neurofilament, and synaptic proteins, resulting from frontal atrophy was detected. In parallel, polymorphic markers on chromosome 17q21-22, the centromeric region of chromosome 3 and chromosome 9, were tested. Haplotype analysis showed several recombination events for chromosomes 3 and 17, but patients shared a haplotype on chromosome 9q21-22. However as one of the patients exhibited Alzheimer and vascular dementia pathology with uncertain concomitant FTD, this locus is questionable. Altogether, these data indicate principally that the Swiss kindred is unlinked to locus 17q21-22, and that tau is not at the origin of FTD in this family.

Study of a Swiss dopa-responsive dystonia family with a deletion in GCH1: redefining DYT14 as DYT5.

OBJECTIVE: To report the study of a multigenerational Swiss family with dopa-responsive dystonia (DRD). METHODS: Clinical investigation was made of available family members, including historical and chart reviews. Subject examinations were video recorded. Genetic analysis included a genome-wide linkage study with microsatellite markers (STR), GTP cyclohydrolase I (GCH1) gene sequencing, and dosage analysis. RESULTS: We evaluated 32 individuals, of whom 6 were clinically diagnosed with DRD, with childhood-onset progressive foot dystonia, later generalizing, followed by parkinsonism in the two older patients. The response to levodopa was very good. Two additional patients had late onset dopa-responsive parkinsonism. Three other subjects had DRD symptoms on historical grounds. We found suggestive linkage to the previously reported DYT14 locus, which excluded GCH1. However, further study with more stringent criteria for disease status attribution showed linkage to a larger region, which included GCH1. No mutation was found in GCH1 by gene sequencing but dosage methods identified a novel heterozygous deletion of exons 3 to 6 of GCH1. The mutation was found in seven subjects. One of the patients with dystonia represented a phenocopy. CONCLUSIONS: This study rules out the previously reported DYT14 locus as a cause of disease, as a novel multiexonic deletion was identified in GCH1. This work highlights the necessity of an accurate clinical diagnosis in linkage studies as well as the need for appropriate allele frequencies, penetrance, and phenocopy estimates. Comprehensive sequencing and dosage analysis of known genes is recommended prior to genome-wide linkage analysis.

Variable phenotypic expressivity in a Swiss family with autosomal dominant retinitis pigmentosa due to a T494M mutation in the PRPF3 gene.

PURPOSE: To characterize the clinical, psychophysical, and electrophysiological phenotypes in a five-generation Swiss family with dominantly inherited retinitis pigmentosa caused by a T494M mutation in the Precursor mRNA-Processing factor 3 (PRPF3) gene, and to relate the phenotype to the underlying genetic mutation. METHODS: Eleven affected patients were ascertained for phenotypic and genotypic characterization. Ophthalmologic evaluations included color vision testing, Goldmann perimetry, and digital fundus photography. Some patients had autofluorescence imaging, Optical Coherence Tomography, and ISCEV-standard full-field electroretinography. All affected patients had genetic testing. RESULTS: The age of onset of night blindness and the severity of the progression of the disease varied between members of the family. Some patients reported early onset of night blindness at age three, with subsequent severe deterioration of visual acuity, which was 0.4 in the best eye after their fifties. The second group of patients had a later onset of night blindness, in the mid-twenties, with a milder disease progression and a visual acuity of 0.8 at age 70. Fundus autofluorescence imaging and electrophysiological and visual field abnormalities also showed some degree of varying phenotypes. The autofluorescence imaging showed a large high-density ring bilaterally. Myopia (range: -0.75 to -8) was found in 10/11 affected subjects. Fundus findings showed areas of atrophy along the arcades. A T494M change was found in exon 11 of the PRPF3 gene. The change segregates with the disease in the family. CONCLUSIONS: A mutation in the PRPF3 gene is rare compared to other genes causing autosomal dominant retinitis pigmentosa (ADRP). Although a T494M change has been reported, the family in our study is the first with variable expressivity. Mutations in the PRPF3 gene can cause a variable ADRP phenotype, unlike in the previously described Danish, English, and Japanese families. Our report, based on one of the largest affected pedigree, provides a better understanding as to the phenotype/genotype description of ADRP caused by a PRPF3 mutation.

The characterization of retinal phenotype in a family with C1QTNF5-related late-onset retinal degeneration.

PURPOSE: To describe the clinical, spectral-domain optical coherence tomography and electrophysiological features of C1QTNF5-associated late-onset retinal degeneration in a molecularly confirmed pedigree. METHODS: Five members of a family participated, and affected individuals (n = 4) underwent detailed ophthalmologic evaluation including fundus autofluorescence and spectral-domain optical coherence tomography imaging and electroretinography. Electrooculography was performed in three individuals. RESULTS: The visual acuity was initially normal and worsened with time. Anterior segment abnormalities included peripupillary iris atrophy and long anterior insertion of zonules. Peripapillary atrophy, drusenoid deposition, and scalloped sectorial chorioretinal atrophy were observed in all older individuals (n = 3). Fundus autofluorescence demonstrated hypofluorescent areas corresponding to regions of chorioretinal atrophy. The spectral-domain optical coherence tomography demonstrated multiple areas of retinal pigment epithelium-Bruch membrane separation with intervening homogeneous deposition that corresponded to the drusenoid lesions and areas of chorioretinal atrophy. Electrooculography was normal in one individual and showed abnormally low dark trough measures in older individuals (n = 2). Electroretinography was normal in early stages (n = 1), but showed marked abnormalities in the rod system (n = 3), which was predominantly inner retinal (n = 2) in late stages. CONCLUSION: Late-onset retinal degeneration is a progressive degeneration, and anterior segment abnormalities present early. The widespread sub-retinal pigment epithelium deposition seen on spectral-domain optical coherence tomography in older individuals appears to be a characteristic in late stages. Electrooculography demonstrates abnormalities only in late stages of the disease.