RESUMO
Aniridia is an autosomal dominant condition characterized by the complete or partial absence of the iris, often with additional presentations such as foveal hypoplasia, nystagmus, cataract, glaucoma and other ocular abnormalities. Most cases are caused by heterozygous mutations in the paired box 6 gene (PAX6), which codes for a transcription factor that regulates eye development. Four patients from our hospital who presented with ocular phenotypes were recruited for research sequencing with informed consent. Sanger sequencing of PAX6 coding exons or exome sequencing was performed on genomic DNA from venous blood samples. Variants in PAX6 were identified in the four patients. Two variants are recurrent single-nucleotide substitutions - one is a substitution found in a patient with bilateral aniridia, whereas the other is a splice variant in a patient with nystagmus and neuroblastoma. The other two variants are novel and found in two patients with isolated aniridia. Both are small duplications that are predicted to lead to premature termination. For the recurrent variants, the comparison of phenotypes for patients with identical variants would shed light on the mechanisms of pathogenesis, and the discovery of two novel variants expands the spectrum of PAX6 mutations.
Assuntos
Aniridia , Catarata , Humanos , Face , Aniridia/genética , Catarata/genética , Éxons , Sudeste Asiático , Fator de Transcrição PAX6/genéticaRESUMO
Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare, autosomal recessive inherited disorder caused by mutations in ROBO3 gene. The clinical features of HGPPS include horizontal gaze palsy, progressive scoliosis, other oculomotor abnormalities such as strabismus and nystagmus. Whole-exome sequencing (WES) is used to diagnose rare Mendelian disorders, when routine standard tests have failed to make a formal pathological diagnosis. However, WES may identify variants of uncertain significance (VUS) that may add further ambiguity to the diagnosis. We report the case of a 4-year-old boy with horizontal gaze palsy, progressive scoliosis, microcephaly, and mild developmental delay. WES identified an intronic VUS in ROBO3 gene. We performed minigene splicing functional analysis to confirm the pathogenicity of this VUS. This report illustrates that WES data analysis with supportive functional analysis provides an effective approach to improve the diagnostic yield for unsolved clinical cases. This case also highlights the phenotypic heterogeneity in patients with HGPPS.
Assuntos
Transtornos da Motilidade Ocular , Oftalmoplegia Externa Progressiva Crônica , Escoliose , Pré-Escolar , Humanos , Masculino , Mutação , Transtornos da Motilidade Ocular/diagnóstico , Transtornos da Motilidade Ocular/genética , Transtornos da Motilidade Ocular/complicações , Oftalmoplegia Externa Progressiva Crônica/diagnóstico , Oftalmoplegia Externa Progressiva Crônica/genética , Receptores de Superfície Celular/genética , Receptores Imunológicos/genética , Proteínas Roundabout , Escoliose/diagnóstico , Escoliose/genética , Escoliose/complicaçõesRESUMO
In this article, we report a case of tuberculosis spondylodiscitis in a 2-year-old child. Imaging of her spine showed a paraspinal abscess. The diagnosis of spinal tuberculosis remains difficult, and we discuss its salient features and current management within the pediatric population.