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Clinical and molecular findings in three Lebanese families with Bietti crystalline dystrophy: report on a novel mutation.

Haddad NM, Waked N, Bejjani R, Khoueir Z, Chouery E, Corbani S, Mégarbané A - Mol. Vis. (2012)

Bottom Line: Two mutations in CYP4V2 were found: p.I111T (c.332T>C) in exon 3 in two families and the novel p.V458M (c.1372G>A) mutation in exon 9 in one family.Variation in disease severity and electroretinographic responses suggests that environmental or additional genetic factors influence the course of the retinal disease.The CYP4V2 p.I111T (c.332T>C) mutant allele may be especially prevalent among patients with BCD in Lebanon, resulting from a single founder.

View Article: PubMed Central - PubMed

Affiliation: Service d’Ophtalmologie, Hôtel-Dieu de France Hospital, Beirut, Lebanon.

ABSTRACT

Purpose: Bietti crystalline dystrophy (BCD) is a rare autosomal recessive disorder caused by mutation of the cytochrome P450, family 4, subfamily V, polypeptide 2 (CYP4V2) gene and characterized by retinal pigmentary abnormalities and scattered deposits of crystals in the retina and the marginal cornea. The aim of this study was to investigate the spectrum of mutations in CYP4V2 in Lebanese families, and to characterize the phenotype of patients affected with BCD.

Methods: Nine patients from three unrelated Lebanese families were clinically and molecularly investigated. Detailed characterization of the patients' phenotype was performed with comprehensive ophthalmic examination, color vision study, fundus photography, visual field testing, retinal fluorescein angiography, electroretinography, and electrooculography. One family was followed for 12 years. The 11 exons of the CYP4V2 gene were sequenced.

Results: Symptoms consisting of night blindness, loss of paracentral visual field, and disturbed color vision were apparent during the third decade of life. Ophthalmoscopy revealed posterior pole crystalline deposits and areas of retinal pigment epithelium atrophy. Fluorescein angiography disclosed geographic areas of the pigment epithelium layer and choriocapillaris atrophy in the posterior pole and fundus periphery. The most striking findings were those of normal electroretinographic responses in some patients and clinical heterogeneity. Two mutations in CYP4V2 were found: p.I111T (c.332T>C) in exon 3 in two families and the novel p.V458M (c.1372G>A) mutation in exon 9 in one family.

Conclusions: These patients are affected with Bietti crystalline dystrophy without corneal involvement. Variation in disease severity and electroretinographic responses suggests that environmental or additional genetic factors influence the course of the retinal disease. The CYP4V2 p.I111T (c.332T>C) mutant allele may be especially prevalent among patients with BCD in Lebanon, resulting from a single founder.

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Related in: MedlinePlus

Electropherogram of the identified mutation: c.1372G>A in the CYP4V2 gene. “Patient Seq” represents the affected individual sequence, homozygous for the mutation compared to the reference sequence “Ref Seq.”
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f3: Electropherogram of the identified mutation: c.1372G>A in the CYP4V2 gene. “Patient Seq” represents the affected individual sequence, homozygous for the mutation compared to the reference sequence “Ref Seq.”

Mentions: The exploration of the entire coding sequence of CYP4V2 in our series allowed identification of the causative mutation in the three families. In family 1, a novel homozygous variation, p.V458M (c.1372G>A), was found in exon 9 in the affected individuals, and at the heterozygous state in their non-affected parents (Figure 3). This mutation was confirmed with polymerase chain reaction-restriction fragment length polymorphism. The 550 bp amplified product was digested by NlaIII producing two fragments of 495 and 93 bp in the affected patients with an undigested product of 545 bp in the heterozygous non-affected individuals.


Clinical and molecular findings in three Lebanese families with Bietti crystalline dystrophy: report on a novel mutation.

Haddad NM, Waked N, Bejjani R, Khoueir Z, Chouery E, Corbani S, Mégarbané A - Mol. Vis. (2012)

Electropherogram of the identified mutation: c.1372G>A in the CYP4V2 gene. “Patient Seq” represents the affected individual sequence, homozygous for the mutation compared to the reference sequence “Ref Seq.”
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3351416&req=5

f3: Electropherogram of the identified mutation: c.1372G>A in the CYP4V2 gene. “Patient Seq” represents the affected individual sequence, homozygous for the mutation compared to the reference sequence “Ref Seq.”
Mentions: The exploration of the entire coding sequence of CYP4V2 in our series allowed identification of the causative mutation in the three families. In family 1, a novel homozygous variation, p.V458M (c.1372G>A), was found in exon 9 in the affected individuals, and at the heterozygous state in their non-affected parents (Figure 3). This mutation was confirmed with polymerase chain reaction-restriction fragment length polymorphism. The 550 bp amplified product was digested by NlaIII producing two fragments of 495 and 93 bp in the affected patients with an undigested product of 545 bp in the heterozygous non-affected individuals.

Bottom Line: Two mutations in CYP4V2 were found: p.I111T (c.332T>C) in exon 3 in two families and the novel p.V458M (c.1372G>A) mutation in exon 9 in one family.Variation in disease severity and electroretinographic responses suggests that environmental or additional genetic factors influence the course of the retinal disease.The CYP4V2 p.I111T (c.332T>C) mutant allele may be especially prevalent among patients with BCD in Lebanon, resulting from a single founder.

View Article: PubMed Central - PubMed

Affiliation: Service d’Ophtalmologie, Hôtel-Dieu de France Hospital, Beirut, Lebanon.

ABSTRACT

Purpose: Bietti crystalline dystrophy (BCD) is a rare autosomal recessive disorder caused by mutation of the cytochrome P450, family 4, subfamily V, polypeptide 2 (CYP4V2) gene and characterized by retinal pigmentary abnormalities and scattered deposits of crystals in the retina and the marginal cornea. The aim of this study was to investigate the spectrum of mutations in CYP4V2 in Lebanese families, and to characterize the phenotype of patients affected with BCD.

Methods: Nine patients from three unrelated Lebanese families were clinically and molecularly investigated. Detailed characterization of the patients' phenotype was performed with comprehensive ophthalmic examination, color vision study, fundus photography, visual field testing, retinal fluorescein angiography, electroretinography, and electrooculography. One family was followed for 12 years. The 11 exons of the CYP4V2 gene were sequenced.

Results: Symptoms consisting of night blindness, loss of paracentral visual field, and disturbed color vision were apparent during the third decade of life. Ophthalmoscopy revealed posterior pole crystalline deposits and areas of retinal pigment epithelium atrophy. Fluorescein angiography disclosed geographic areas of the pigment epithelium layer and choriocapillaris atrophy in the posterior pole and fundus periphery. The most striking findings were those of normal electroretinographic responses in some patients and clinical heterogeneity. Two mutations in CYP4V2 were found: p.I111T (c.332T>C) in exon 3 in two families and the novel p.V458M (c.1372G>A) mutation in exon 9 in one family.

Conclusions: These patients are affected with Bietti crystalline dystrophy without corneal involvement. Variation in disease severity and electroretinographic responses suggests that environmental or additional genetic factors influence the course of the retinal disease. The CYP4V2 p.I111T (c.332T>C) mutant allele may be especially prevalent among patients with BCD in Lebanon, resulting from a single founder.

Show MeSH
Related in: MedlinePlus