A Case of Trisomy 13 Mosaicism Presenting with a Severe Aortic Root Dilatation and Marfanoid Habitus due to an Unpredictable Cytogenetic Mechanism.

In this report, we present a new case of mosaic trisomy 13 with prolonged survival, firstly detected by array-CGH analysis which was carried out because of moderate intellectual disability with postaxial hexadactyly, dermatologic features, ventricular septal defect, bicuspid aortic valve, and aortic dystrophy in a 19-year-old male patient. In a subset of 15% of the cells, the patient carried a derivative chromosome 10 generated by a nonreciprocal (10;13) translocation inherited from his healthy mother who carried the translocation in a balanced and homogeneous state. FISH analyses showed interstitial telomeric sequences at the breakpoints. To our knowledge, this is the second report of a patient with trisomy 13 mosaicism displaying a severe aortic root dilatation. We also discuss the mechanisms which could explain the mosaic state, the most likely one being related to the instability of the interstitial telomere.

Classifying Ectopia Lentis in Marfan Syndrome into Five Grades of Increasing Severity.

PURPOSE: To describe a five-grade classification of ectopia lentis in Marfan syndrome (MFS) and to evaluate the positive predictive value of the early grades of ectopia lentis. METHODS: We prospectively included MFS patients and their healthy relatives. The anterior segment examination was classified into grades 0 to 5, and we studied the sensitivity, specificity, and positive predictive value of ectopia lentis in this classification. RESULTS: Seventy-four MFS patients and thirty-six healthy controls were examined. In the MFS group, grades 1, 2, 3, and 4 were present in 15, 24, 17, and 7 patients, respectively, whereas 11 patients in this group did not present ectopia lentis. In the control group, grades 0 and 1 were observed in 30 and 6 individuals, respectively. Sensitivity to ectopia lentis of at least grade 2 was 64.9%, with 100% specificity, whereas sensitivity to ectopia lentis of at least grade 1 was 85.1%, with 83.3% specificity. The positive predictive value of ectopia lentis that was greater than or equal to grade 2 was 100%, whereas that of ectopia lentis greater than or equal to grade 1 was 91.3%. CONCLUSION: High positive predictive values s were found to be associated with grades 2 and higher of the five-grade classification of ectopia lentis. This classification should help to harmonize clinical practices for this major feature of MFS.

Physical and transcript map of the autosomal dominant colobomatous microphthalmia locus on chromosome 15q12-q15 and refinement to a 4.4 Mb region.

Congenital microphthalmia is a developmental disorder characterized by shortened axial length of the eye. We have previously mapped the gene responsible for autosomal dominant colobomatous microphthalmia in a 5-generation family to chromosome 15q12-q15. Here, we set up a physical and transcript map of the 13.8 cM critical region, flanked by loci D15S1002 and D15S1040. Physical mapping and genetic linkage analysis using 20 novel polymorphic markers allowed the refinement of the disease locus to two intervals in close vicinity, namely a centromeric interval, bounded by microsatellite DNA markers m3-m17, and a telomeric interval, m76-m24, encompassing respectively 1.9 and 2.5 Mb. Moreover, we excluded three candidate genes, CKTSF1B1, KLF13 and CX36. Finally, although a phenomenon of anticipation was suggested by phenotypic and pedigree data, no abnormal expansion of three trinucleotide repeats mapping to the refine interval was found in affected individuals.

[Risk factors for secondary retinal detachment after extraction of intraocular foreign bodies]. / Facteurs de risque de décollement de rétine après extraction de corps étrangers intraoculaires.

BACKGROUND: Better identification of patients at risk for retinal detachment after intraocular foreign body removal would guide management as well as help prevent this complication. We performed a study to identify risk factors for secondary retinal detachment in eyes with retained intraocular foreign bodies. METHODS: We reviewed the records of 102 consecutive patients (95 males and 7 females with a mean age of 31.6 years) seen between 1990 and 1995 at one ophthalmology service for intraocular foreign body after penetrating ocular injury. All eyes underwent primary surgical repair and foreign body removal (via electromagnet or vitrectomy). The mean length of follow-up was 2 years (range 6 months to 6 years). Survival analysis (Kaplan-Meier, Cox regression) was performed to determine predictors of retinal detachment. RESULTS: The foreign body was metallic in 95% of cases and magnetic in 60%. The largest diameter was 3 mm or more in 35% of cases (range 1 mm to 25 mm, mean 3.6 mm). The foreign body was preretinal or intraretinal in 24 patients (24%), intravitreal in 47 (46%), located in the sclera in 16 (16%) and located in the anterior segment in 15 (15%). A secondary retinal detachment developed in 25 patients (24%) after foreign body removal, with a mean delay of 4.6 (standard deviation 7.6) months (range 7 days to 31 months). The posterior pole was detached in 15 patients (60%). The retinal detachment was total in 13 patients (52%). Proliferative vitreoretinopathy was noted in 13 cases (grade B in 3, grade CI in 3, grade CI in 1, grade C3 in 1, and grade C4 in 5). Univariate analysis using Kaplan-Meier survival showed that firearm injuries, visual acuity less than 20/200, presence of hyphema, presence of tissue prolapse and presence of vitreous hemorrhage at the initial examination were significantly associated with the occurrence of secondary retinal detachment. On multivariate analysis (Cox regression), two independent and combined factors were predictive of retinal detachment: initial visual acuity less than 20/200 (odds ratio 5.5, p = 0.02) and presence of vitreous hemorrhage (odds ratio 2.2, p = 0.05). INTERPRETATION: Patients at risk for secondary retinal detachment after penetrating ocular injury with retained intraocular foreign body can be identified at the initial examination.

Novel VCAN mutations and evidence for unbalanced alternative splicing in the pathogenesis of Wagner syndrome.

Wagner syndrome (WS) is an autosomal dominant vitreoretinopathy affecting various ocular features and is caused by mutations in the canonical splice sites of the VCAN gene, which encodes the large chondroitin sulfate proteoglycan, versican. We report the identification of novel splice acceptor and donor-site mutations (c.4004-1G>C and c.9265+2T>A) in two large WS families from France and the United Kingdom. To characterize their pathogenic mechanisms we performed qRT-PCR experiments on RNA from patient-derived tissues (venous blood and skin fibroblasts). We also analyzed RNA from the original Swiss family reported by Wagner (who has the previously reported c.9265+1G>A mutation). All three mutations resulted in a quantitative increase of transcript variants lacking exons 7 and/or 8. However, the magnitude of the increase varied between tissues and mutations. We discuss altered balance of VCAN splice variants in combination with reduction in glycosaminoglycan protein modifications as possible pathogenic mechanisms.