A missense point mutation (Leu13Arg) of the Norrie disease gene in a large Cuban kindred with Norrie disease

Fuchs, Sigrid; Xu, Shijun; Caballero, Manuel; Salcedo, Mauricio; Wedemann, Heike; Gal, A.

doi:10.1093/hmg/3.4.655

Cited by 18 publications

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“…The phenotype has often been described in general terms, such as ‘mental retardation’. For example, in a large Cuban kindred with 46 affected members, 45% of the examined patients were described to show moderate or severe mental retardation (Fuchs et al. , 1994).…”

Section: Discussionmentioning

confidence: 99%

Vascular changes in the cerebellum of Norrin /Ndph knockout mice correlate with high expression of Norrin and Frizzled‐4

Luhmann

Neidhardt

Kloeckener-Gruissem

et al. 2008

Eur J of Neuroscience

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X-linked Norrie disease, familial exudative vitreoretinopathy (FEVR), Coat's disease and retinopathy of prematurity are severe human eye diseases and can all be caused by mutations in the Norrie disease pseudoglioma gene. They all show vascular defects and characteristic features of retinal hypoxia. Only Norrie disease displays additional neurological symptoms, which are sensorineural hearing loss and mental retardation. In the present study, we analysed transcript levels of the ligand Norrin (Ndph) and its two receptors Frizzled-4 (Fzd4) and LDL-related protein receptor 5 (Lrp5) in six different brain regions (cerebellum, cortex, hippocampus, olfactory bulb, pituitary and brain stem) of 6- to 8-month-old wild-type and Ndph knockout mice by quantitative real-time PCR. No effect of the Ndph knockout allele on Fzd4 or Lrp5 receptor expression was found. Furthermore, no alterations of the transcript levels of three hypoxia-regulated angiogenic factors (Vegfa, Itgrb3 and Tie1) were observed in the absence of Norrin. Interestingly, we identified significant differences in Ndph, Fzd4 and Lrp5 transcript levels in brain regions of wild-type mice and observed highest expression of Norrin and frizzled-4 in cerebellum. Transcript analyses were correlated with morphological data obtained from cerebellum and immunohistochemical studies of blood vessels in different brain regions. Vessel density was reduced in the cerebellum of Ndph knockout mice but the number of Purkinje and granular cells was not altered. This provides the first description of a brain phenotype in Ndph knockout mice, which will help to elucidate the role of Norrin in the brain.

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Section: Discussionmentioning

confidence: 99%

Vascular changes in the cerebellum of Norrin /Ndph knockout mice correlate with high expression of Norrin and Frizzled‐4

Luhmann

Neidhardt

Kloeckener-Gruissem

et al. 2008

Eur J of Neuroscience

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“…Parental analysis showed that this mutation appeared de novo . A mutation affecting the same Leu13 amino acid (p.Leu13Arg) has been described previously in a family in which 45% of the affected members displayed moderate or severe intellectual disability. Due to the potential severity of ND, and after the couple received all the necessary information, they requested medical termination of the pregnancy, which was accepted by the multidisciplinary prenatal diagnosis center.…”

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confidence: 99%

Prenatal diagnosis of Norrie disease based on ultrasound findings

Dubucs

Merveille²,

Kessler³

et al. 2019

Ultrasound in Obstet & Gyne

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Norrie disease (ND; OMIM: 310600) is a rare, X-linked, recessive genetic disease caused by mutations in the NDP gene and characterized by congenital blindness due to bilateral degenerative changes in neuroretina. About half of ND patients have intellectual disability. ND first manifests by ocular features during the third trimester of pregnancy after normal scan findings of the first two trimesters of pregnancy. This article is protected by copyright. All rights reserved.

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“…Numerous point mutations have been detected, which lead to truncated or elongated gene products, but more frequently to amino acid substitutions (15)(16)(17)(18). These studies also revealed that not only the ocular symptoms, but also mental disturbances and deafness are pleiotropic effects of a single mutation (15) and that a less severe condition, X-linked familial exudative vitreoretinopathy, is allelic to ND (19).…”

Section: Introductionmentioning

confidence: 99%

An animal model for Norrie disease (ND): gene targeting of the mouse ND gene

1996

Trends in Genetics

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Please be advised that this information was generated on 2018-05-09 and may be subject to change. © 1996 Oxfo rd Uni vet \s ita > PressHuman Molecular Genetics, 7996, Vol. 5 In order to elucidate the cellular and molecular processes which are involved in Norrie disease (NO), we have used gene targeting technology to generate ND mutant mice. The murine homologue of the ND gene was cloned and shown to encode a polypeptide that shares 94% of the amino acid sequence with its human counterpart. RNA in situ hybridization revealed expression in retina, brain and the olfactory bulb and epithelium of 2 week old mice. Hemizygous mice carrying a replacement mutation in exon 2 of the ND gene developed retrolental structures in the vitreous body and showed an overall disorganization of the retinal ganglion cell layer. The outer plexiform layer disappears occasionally, resulting in a juxtaposed inner and outer nuclear layer. At the same regions, the outer segments of the photoreceptor cell layer are no longer present. These ocular findings are consistent with observations in ND patients and the generated mouse line provides a faithful model for study of early pathogenic events in this severe X-linked recessive neurological disorder.

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A missense point mutation (Leu13Arg) of the Norrie disease gene in a large Cuban kindred with Norrie disease

Cited by 18 publications

References 0 publications

Vascular changes in the cerebellum of Norrin /Ndph knockout mice correlate with high expression of Norrin and Frizzled‐4

Vascular changes in the cerebellum of Norrin /Ndph knockout mice correlate with high expression of Norrin and Frizzled‐4

Prenatal diagnosis of Norrie disease based on ultrasound findings

An animal model for Norrie disease (ND): gene targeting of the mouse ND gene

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