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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

Numerous retinal crystals and chorioretinal atrophy are visible on the fundus photos of the patients with Bietti crystalline corneoretinal dystrophy.
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f2: Numerous retinal crystals and chorioretinal atrophy are visible on the fundus photos of the patients with Bietti crystalline corneoretinal dystrophy.

Mentions: Fifteen patients were examined in total. Nine patients were affected, and the remaining six asymptomatic individuals were examined in the genetic counseling setting. The clinical findings from the nine affected patients are summarized in Table 2. Eight were female. Two were asymptomatic, three had visual complaints related to nyctalopia, and four complained of decreased visual acuity (VA). Three of the patients had blindness, while in the others, visual acuity was preserved even in severe cases since the central vision had remained normal at first particularly for near, before decreasing gradually. Best-corrected visual acuity (BCVA) in these individuals ranged from light perception to Snellen 20/20. Color vision testing using Ishihara plates ranged between normal and severe color vision deficiency. Automated visual fields when performed gave results ranging between paracentral scotoma and severe uniform alteration. The slit lamp exam did not show any corneal deposits, and the anterior segments were within normal limits in all examined patients. Fundus photos showed chorioretinal atrophy in all affected patients and crystalline deposits in some cases (Figure 2). When performed, electroretinography (ERG) remained within normal limits, and electrooculography (EOG) showed an additional decrease in the Arden ratio that was either moderately or severely affected.


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)

Numerous retinal crystals and chorioretinal atrophy are visible on the fundus photos of the patients with Bietti crystalline corneoretinal dystrophy.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: Numerous retinal crystals and chorioretinal atrophy are visible on the fundus photos of the patients with Bietti crystalline corneoretinal dystrophy.
Mentions: Fifteen patients were examined in total. Nine patients were affected, and the remaining six asymptomatic individuals were examined in the genetic counseling setting. The clinical findings from the nine affected patients are summarized in Table 2. Eight were female. Two were asymptomatic, three had visual complaints related to nyctalopia, and four complained of decreased visual acuity (VA). Three of the patients had blindness, while in the others, visual acuity was preserved even in severe cases since the central vision had remained normal at first particularly for near, before decreasing gradually. Best-corrected visual acuity (BCVA) in these individuals ranged from light perception to Snellen 20/20. Color vision testing using Ishihara plates ranged between normal and severe color vision deficiency. Automated visual fields when performed gave results ranging between paracentral scotoma and severe uniform alteration. The slit lamp exam did not show any corneal deposits, and the anterior segments were within normal limits in all examined patients. Fundus photos showed chorioretinal atrophy in all affected patients and crystalline deposits in some cases (Figure 2). When performed, electroretinography (ERG) remained within normal limits, and electrooculography (EOG) showed an additional decrease in the Arden ratio that was either moderately or severely affected.

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