The importance of biochemical and genetic findings in the diagnosis of atypical Norrie disease
| Autor: | José M. Millán, Menor F, Gema García-García, Ana Rodríguez-Muñoz, Miguel Tomás-Vila, Teresa Jaijo |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Biogenic Amines medicine.medical_specialty Pathology Adolescent Microarray brain and cerebellar atrophy Clinical Biochemistry Nerve Tissue Proteins Disease Blindness Eye medicine.disease_cause Contiguous gene syndrome 03 medical and health sciences Exon 0302 clinical medicine Cerebellum Internal medicine contiguous gene syndrome medicine Humans monoamine oxidase Eye Proteins Monoamine Oxidase Gene Cerebral Cortex Neurotransmitter Agents Mutation business.industry Retinal Degeneration Biochemistry (medical) Genetic Diseases X-Linked General Medicine medicine.disease Phenotype Norrie disease 030104 developmental biology Endocrinology Child Preschool 030221 ophthalmology & optometry psychomotor regression Nervous System Diseases business Spasms Infantile Gene Deletion |
| Zdroj: | CLINICAL CHEMISTRY AND LABORATORY MEDICINE r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe instname |
| ISSN: | 1437-4331 1434-6621 |
| DOI: | 10.1515/cclm-2017-0226 |
| Popis: | Background: Norrie disease (ND) is a rare X-linked disorder characterized by bilateral congenital blindness. ND is caused by a mutation in the Norrie disease pseudoglioma (NDP) gene, which encodes a 133-amino acid protein called norrin. Intragenic deletions including NDP and adjacent genes have been identified in ND patients with a more severe neurologic phenotype. We report the biochemical, molecular, clinical and radiological features of two unrelated affected males with a deletion including NDP and MAO genes. Methods: Biochemical and genetic analyses were performed to understand the atypical phenotype and radiological findings. Biogenic amines in cerebrospinal fluid (CSF) were measured by high-performance liquid chromatography. The coding exons of NDP gene were amplified by polymerase chain reaction. Multiplex ligation-dependent probe amplification and chromosomal microarray were carried out on both affected males. Computed tomography and magnetic resonance imaging were performed on the two patients. Results: In one patient, the serotonin and catecholamine metabolite levels in CSF were virtually undetectable. In both patients, genetic studies revealed microdeletions in the Xp11.3 region, involving the NDP, MAOA and MAOB genes. Radiological examination demonstrated brain and cerebellar atrophy. Conclusions: We suggest that alterations caused by MAO deficit may remain during the first years of life. Clinical phenotype, biochemical findings and neuroimaging can guide the genetic study in patients with atypical ND and help us to a better understanding of this disease. |
| Databáze: | OpenAIRE |
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