Two novel mutations in the Norrie disease gene associated with the classical ocular phenotype

Caballero, Manuel; Veske, Andres; Rodríguez, Juan José Tavárez; Lugo, Noel Taboada; Schroêder, B.; Hesse, Lutz; Gal, A.

doi:10.3109/13816819609057892

Cited by 5 publications

(2 citation statements)

References 19 publications

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“…PHARC syndrome, characterized by polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataracts, is notable for its variable age at onset of polyneuropathy ( Frasquet et al 2018 ). Norrie's disease, caused by a variant on the X chromosome, frequently presents as congenital retinal degeneration and proliferation which progresses to retinal detachment, with hearing loss manifesting in a roughly estimated 25%–33% of these individuals ( Caballero et al 1996 ; Warburg 1966 ). PRPS1 variants result in three distinct disorders, all of which present with hearing loss as a common feature ( Almoguera et al 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Hiding in plain sight: genetic deaf-blindness is not always Usher syndrome

Medina

Perry

Oza

et al. 2021

Cold Spring Harb Mol Case Stud

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Introduction: Hearing loss (HL) is the most common congenital sensory impairment. Usher syndrome (USH) is the leading genetic etiology of congenital deafness combined with progressive vision loss, and individuals presenting with these symptoms are often assumed to have USH. This can be an erroneous assumption, as there are additional genetic causes of deafblindness.Objective: To describe and accurately diagnose non-USH genetic causes of deaf-blindness.Methods: We present three children with hearing and vision loss with clinical and genetic findings suggestive of USH. However, ongoing clinical assessment did not completely support an USH diagnosis, and exome analysis was pursued for all three individuals.Results: Updated genetic testing showed pathogenic variants in ALMS1 in the first individual and TUBB4B in the second and third. Although HL in all three was consistent with USH type 2, vision impairment with retinal changes was noted by age two years, which is unusual for USH.In all three the updated genotype more accurately fit the clinical phenotype. Conclusion:Because USH is the most common form of genetic deaf-blindness, individuals with HL, early vision impairment, and retinal dysfunction are often assumed to have USH. However, additional genes associated with HL and retinal impairment include ALMS1, TUBB4B, CEP78, ABHD12, and PRPS1. Accurate genetic diagnosis is critical to these individuals' understanding of their genetic conditions, prognosis, vision and hearing loss management, and future access to molecular therapies. If clinically or genetically USH seems uncertain, updated genetic testing for non-USH genes is essential.

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Section: Discussionmentioning

confidence: 99%

Hiding in plain sight: genetic deaf-blindness is not always Usher syndrome

Medina

Perry

Oza

et al. 2021

Cold Spring Harb Mol Case Stud

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“…As the translation start site and its context sequence play an important role in the control of translation efficiency and the correct translation of mRNA, the c.2T>A mutation is expected to cause the failure of the start of ND gene translation or the production of an aberrant protein. Previous reported initiation codon point mutations, c.1_2delAAT, c.2_3delTG, c.1A>G (p.Met1Val) and c.2T>G (p.Met1Arg), have been reported to be responsible for ND (Isashiki et al 1995;Schuback et al 1995;Caballero et al 1996;Zhang et al 2013). All these patients have congenital blindness.…”

Section: Referencesmentioning

confidence: 96%

A novel c.2T>A NDP missense mutation in a Chinese family with Norrie disease

Huang

2015

Acta Ophthalmologica

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Overview of the mutation spectrum in familial exudative vitreoretinopathy and Norrie disease with identification of 21 novel variants in FZD4, LRP5, and NDP

et al. 2010

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Wnt signaling is a crucial component of the cell machinery orchestrating a series of physiological processes such as cell survival, proliferation, and migration. Among the plethora of roles that Wnt signaling plays, its canonical branch regulates eye organogenesis and angiogenesis. Mutations in the genes encoding the low density lipoprotein receptor protein 5 (LRP5) and frizzled 4 (FZD4), acting as coreceptors for Wnt ligands, cause familial exudative vitreoretinopathy (FEVR). Moreover, mutations in the gene encoding NDP, a ligand for these Wnt receptors, cause Norrie disease and FEVR. Both FEVR and Norrie disease share similar phenotypic characteristics, including abnormal vascularization of the peripheral retina and formation of fibrovascular masses in the eye that can lead to blindness. In this mutation update, we report 21 novel variants for FZD4, LRP5, and NDP, and discuss the putative functional consequences of missense mutations. In addition, we provide a comprehensive overview of all previously published variants in the aforementioned genes and summarize the phenotypic characteristics in mouse models carrying mutations in the orthologous genes. The increasing molecular understanding of Wnt signaling, related to ocular development and blood supply, offers more tools for accurate disease diagnosis that may be important in the development of therapeutic interventions.

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Two novel mutations in the Norrie disease gene associated with the classical ocular phenotype

Cited by 5 publications

References 19 publications

Hiding in plain sight: genetic deaf-blindness is not always Usher syndrome

Hiding in plain sight: genetic deaf-blindness is not always Usher syndrome

A novel c.2T>A NDP missense mutation in a Chinese family with Norrie disease

Overview of the mutation spectrum in familial exudative vitreoretinopathy and Norrie disease with identification of 21 novel variants in FZD4, LRP5, and NDP

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