The importance of biochemical and genetic findings in the diagnosis of atypical Norrie disease

Data de publicació: 01/02/2018

Autors de IIS La Fe

Ana Rodríguez Muñóz

Autor
Gema García García

Autor
Francisco Menor Serrano

Autor
José María Millán Salvador

Autor
Miguel Tómas Vila

Autor
Teresa Jaijo Sanchís

Autor

Grups d'Investigació

Biomedicina Molecular, Celular y Genómica

Leader

José María Millán Salvador
Unidad mixta de investigación en enfermedades raras (CIPF)

Leader

José María Millán Salvador

Abstract

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.

Dades de la publicació

ISSN/ISSNe:: 1434-6621, 1437-4331
Tipus:: Article
Pàgines:: 229-235
DOI:: 10.1515/cclm-2017-0226
PubMed:: 28742514
Factor d'Impacte:: 1,191 SCImago ℠
Quartil:: Q1 SCImago ℠

Documents

No hi ha documents

Mètriques

Filiacions

Rodriguez-Munoz, A:: Instituto de Investigación. Inst Invest Sanitaria La Fe, Grp Invest Biomed Mol Celular & Genom, Valencia, Spain
Garcia-Garcia, G:: Instituto de Investigación. Inst Invest Sanitaria La Fe, Grp Invest Biomed Mol Celular & Genom, Valencia, Spain

CIBERER, Valencia, Spain
Menor, F:: Hosp Univ & Politecn La Fe, Radiol Infantil, Valencia, Spain
Millan, JM:: Instituto de Investigación. Inst Invest Sanitaria La Fe, Grp Invest Biomed Mol Celular & Genom, Valencia, Spain

CIBERER, Valencia, Spain
Tomas-Vila, M:: Hosp Univ & Politecn La Fe, Neuropediat, Valencia, Spain
Jaijo, T:: Instituto de Investigación. Inst Invest Sanitaria La Fe, Grp Invest Biomed Mol Celular & Genom, Valencia, Spain

CIBERER, Valencia, Spain

Hosp Univ & Politecn La Fe, Unidad Genet & Diagnost Prenatal, Valencia, Spain

Keywords

brain and cerebellar atrophy; contiguous gene syndrome; monoamine oxidase; Norrie disease; psychomotor regression

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