RESUMO
Autosomal recessive retinitis pigmentosa (arRP) is a clinically and genetically heterogeneous retinal disease that causes blindness. Our purpose was to identify the causal gene, describe the phenotype and delineate the mutation spectrum in a consanguineous Quebec arRP family. We performed Arrayed Primer Extension (APEX) technology to exclude â¼500 arRP mutations in â¼20 genes. Homozygosity mapping [single nucleotide polymorphism (SNP) genotyping] identified 10 novel significant homozygous regions. We performed next generation sequencing and whole exome capture. Sanger sequencing provided cosegregation. We screened another 150 retinitis pigmentosa (RP) and 200 patients with Senior-Løken Syndrome (SLS). We identified a novel missense mutation in WDR19, c.2129T>C which lead to a p.Leu710Ser. We found the same mutation in a second Quebec arRP family. Interestingly, two of seven affected members of the original family developed 'sub-clinical' renal cysts. We hypothesized that more severe WDR19 mutations may lead to severe ciliopathies and found seven WDR19 mutations in five SLS families. We identified a new gene for both arRP and SLS. WDR19 is a ciliary protein associated with the intraflagellar transport machinery. We are currently investigating the full extent of the mutation spectrum. Our findings are crucial in expanding the understanding of childhood blindness and identifying new genes.
Assuntos
Genes Recessivos , Doenças Renais Císticas/genética , Amaurose Congênita de Leber/genética , Mutação , Atrofias Ópticas Hereditárias/genética , Proteínas/genética , Retinose Pigmentar/genética , Adolescente , Adulto , Criança , Pré-Escolar , Ciliopatias , Consanguinidade , Proteínas do Citoesqueleto , Exoma , Feminino , Estudos de Associação Genética , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND AND PURPOSE: Despite the benign histology of optic pathway glioma (OPG) (low-grade astrocytoma), its biological behavior is unpredictable, and it is unclear whether specific morphologic or anatomic patterns may be predictive of prognosis. It is also unclear whether OPG associated with neurofibromatosis (NF) is a distinct entity from non-NF-OPG. Our purpose was to describe the MR imaging features of OPG, compare the findings between patients with and those without NF, and identify prognostic imaging signs. METHODS: MR examinations of 91 patients with OPG (47 with NF and 44 without) were reviewed at presentation and during follow-up. The images were evaluated for size and extension of tumor, and imaging parameters. Statistical bivariate analysis was used to compare the patients with and those without NF, and Pearson correlation was used to evaluate the correlation between the different imaging parameters and prognosis. Kappa values were calculated to determine intraobserver and interobserver variability. RESULTS: The most common site of involvement in the NF group was the orbital nerve (66%), followed by the chiasm (62%). In the non-NF group, the chiasm was the most common site of involvement (91%); the orbital nerves were involved in only 32%. Extension beyond the optic pathway at diagnosis was uncommon in the NF group (2%) but frequent in the non-NF group (68%). In the NF group, the tumor was smaller and the original shape of the optic pathways was preserved (91% vs. 27% in the non-NF group). The presence of cystic components was significantly more common in the non-NF patients (66% vs. 9% in the NF group). During follow-up, half the NF patients remained stable, in contrast to 5% of the non-NF group. No statistical correlation was found between imaging features and biological behavior of the tumor. CONCLUSION: NF-OPG is a separate entity from non-NF-OPG, with different imaging features and prognosis, thereby warranting a specific diagnostic, clinical, and therapeutic approach.
Assuntos
Glioma/diagnóstico , Neoplasias Hipotalâmicas/diagnóstico , Neurofibromatoses/complicações , Glioma do Nervo Óptico/diagnóstico , Vias Visuais , Adolescente , Criança , Pré-Escolar , Feminino , Glioma/complicações , Humanos , Neoplasias Hipotalâmicas/complicações , Lactente , Imageamento por Ressonância Magnética , Masculino , Quiasma Óptico , Glioma do Nervo Óptico/complicaçõesRESUMO
Torsion of the testis and torsion of the testicular appendages have similar presenting features, namely, acute testicular pain and swelling. The former condition requires urgent surgical intervention to save the testis; the latter condition can be treated conservatively. Despite the frequency of torsion of the appendix testis, which is the most common cause of acute hemiscrotum in the child, only occasional references to this entity are found in the radiological literature. We describe five cases in which an enlarged, homogeneously echogenic appendix testis was seen medial or posterior to the head of the epididymis. All cases were accompanied by hydrocele and thickening of the scrotal wall. Among the five cases, enlargement of the head of the epididymis was seen in four and increased testicular blood flow in two. Scanning in the coronal and transverse planes above the testis was useful in locating the enlarged, twisted appendix.