Two new missense mutations (A105T and C110G) in the Norrin gene in two Italian families with Norrie disease and familial exudative vitreoretinopathy

Torrente, Isabella; Mangino, Massimo; Gennarelli, Massimo; Novelli, Giuseppe; Giannotti, Aldo; Vadala, P.; Dallapiccola, Bruno

doi:10.1002/(sici)1096-8628(19971017)72:2<242::aid-ajmg23>3.0.co;2-m

Cited by 18 publications

(13 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To our knowledge the Leu103Val mutation in exon 3 has not been previously described. Mutations in this region include Lys104Gln and Ala105Thr in less severe Norrie disease patients 25,26 . Other NDP gene mutations identified in X‐linked FEVR patients were also located in exon 3, at amino acid positions 121 and 124 1,27 …”

Section: Discussionmentioning

confidence: 99%

Mutations in the NDP gene: contribution to Norrie disease, familial exudative vitreoretinopathy and retinopathy of prematurity

Dickinson

Sale

Passmore

et al. 2006

Clinical Exper Ophthalmology

View full text Add to dashboard Cite

Two novel mutations within the coding region of the NDP gene were found, one associated with a severe disease phenotypes of Norrie disease and the other with FEVR. A deletion within the non-coding region was associated with only mild-regressed ROP, despite the presence of low birthweight, prematurity and exposure to oxygen. In full-term children with retinal detachment only 15% appear to have the full features of Norrie disease and this is important for counselling parents on the possible long-term outcome.

show abstract

Section: Discussionmentioning

confidence: 99%

Mutations in the NDP gene: contribution to Norrie disease, familial exudative vitreoretinopathy and retinopathy of prematurity

Dickinson

Sale

Passmore

et al. 2006

Clinical Exper Ophthalmology

View full text Add to dashboard Cite

show abstract

“…Study of ND mutant mice revealed retrolental structures in the vitreous body and overall disorganization of the retinal ganglion cell layer, also suggesting its functions in the regulation of neural cell differentiation and proliferation [Berger et al, 1996]. A number of base substitutions and deletions in NDP have been reported in ND patients [Isashiki et al, 1995; Meindl et al, 1995; Schuback et al, 1995; Torrente et al, 1997], in cases of X‐linked and sporadic exudative vitreoretinopathy [Chen et al, 1993b; Shastry et al, 1997a; Torrente et al, 1997], in retinopathy of prematurity [Shastry et al, 1997b], and in Coats disease [Black et al, 1999]. Though phenotypic variability was documented between affected individuals even within a family [Zeremba et al, 1998], a genotype‐phenotype correlation remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Two Thai families with Norrie disease (ND): Association of two novel missense mutations with severe ND phenotype, seizures, and a manifesting carrier

et al. 2001

View full text Add to dashboard Cite

We describe two Thai families with Norrie disease (ND) in three generations, including 10 affected males and one manifesting female. All affected males in each family had severely defective eye development with complete loss of vision. In addition, three male patients (one from family 1 and two from family 2) suffered from epilepsy, and one female carrier from one family manifested blindness with phthisis bulbi in her right eye. Mutation analysis of the ND gene (NDP) revealed two different novel missense mutations (L16P and S75P) that co-segregated with ND in each family, suggesting that the newly appearing proline at codon 16 or codon 75 alters the conformation of the ND protein and contributes to the severe phenotype of ND in each family. Other studies suggest that epileptic seizures or growth retardation that is associated with ND is the consequence of loss of contiguous genes, because most such patients had deletions extending beyond the Norrie locus. Our finding that the three affected males in the two families with the missense mutations had epilepsy does not support a contiguous gene effect, but favors the pleiotropism of NDP, at least as far as the epileptic manifestation is concerned. The unilateral blindness in the female carrier may have been due to non-random X-inactivation.

show abstract

“…Similarly, the p.(Ala105Phe) found in family 5 lies in a mutational hot spot since two other variants in the same codon, namely, the p.(Ala105Thr) and the p.(Ala105Glu), were described as associated with Norrie Disease [13] and FEVR [41], respectively.…”

Section: Discussionmentioning

confidence: 99%

“…In literature on Italian FEVR patients, only three genetic association studies describing a total of six probands are reported [13–15]. Here, we present the results of clinical and genetic characterization of the largest Italian FEVR population, consisting of six probands and ten relatives, as a contribution to the FEVR disease molecular epidemiology in our country.…”

Section: Introductionmentioning

confidence: 93%

Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy

Iarossi

Bertelli²,

Maltese³

et al. 2017

Journal of Ophthalmology

View full text Add to dashboard Cite

Familial exudative vitreoretinopathy (FEVR) is a complex disorder characterized by incomplete development of the retinal vasculature. Here, we report the results obtained on the spectrum of genetic variations and correlated phenotypes found in a cohort of Italian FEVR patients. Eight probands (age range 7–19 years) were assessed by genetic analysis and comprehensive age-appropriate ophthalmic examination. Genetic testing investigated the genes most widely associated in literature with FEVR: FZD4, LRP5, TSPAN12, and NDP. Clinical and genetic evaluations were extended to relatives of probands positive to genetic testing. Six out of eight probands (75%) showed a genetic variation probably related to the phenotype. We identified four novel genetic variants, one variant already described in association with Norrie disease and one previously described linked to autosomal dominant FEVR. Pedigree analysis of patients led to the classification of four autosomal dominant cases of FEVR (caused by FZD4 and TSPAN12 variants) and two X-linked FEVR probands (NDP variants). None of the patients showed variants in the LRP5 gene. This study represents the largest cohort study in Italian FEVR patients. Our findings are in agreement with the previous literature confirming that FEVR is a clinically and genetically heterogeneous retinal disorder, even when it manifests in the same family.

show abstract

Two new missense mutations (A105T and C110G) in the Norrin gene in two Italian families with Norrie disease and familial exudative vitreoretinopathy

Cited by 18 publications

References 13 publications

Mutations in the NDP gene: contribution to Norrie disease, familial exudative vitreoretinopathy and retinopathy of prematurity

Mutations in the NDP gene: contribution to Norrie disease, familial exudative vitreoretinopathy and retinopathy of prematurity

Two Thai families with Norrie disease (ND): Association of two novel missense mutations with severe ND phenotype, seizures, and a manifesting carrier

Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy

Contact Info

Product

Resources

About