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Five novel CNGB3 gene mutations in Polish patients with achromatopsia.

Wawrocka A, Kohl S, Baumann B, Walczak-Sztulpa J, Wicher K, Skorczyk-Werner A, Krawczynski MR - Mol. Vis. (2014)

Bottom Line: We also found three mutations: one splice site (c.1578+1G>A) and two frame-shift deletions that had been previously described (c.819_826del and c.1148delC).The present study reports five novel mutations in the CNGB3 gene, and thus broadens the spectrum of probably pathogenic mutations associated with ACHM.Together with molecular data, we provide a brief clinical description of the affected individuals.

View Article: PubMed Central - PubMed

Affiliation: Chair and Department of Medical Genetics, Poznan University of Medical Science, Poland.

ABSTRACT

Purpose: To identify the genetic basis of achromatopsia (ACHM) in four patients from four unrelated Polish families.

Methods: In this study, we investigated probands with a clinical diagnosis of ACHM. Ophthalmologic examinations, including visual acuity testing, color vision testing, and full-field electroretinography (ERG), were performed in all patients (with the exception of patient p4, who had no ERG). Direct DNA sequencing encompassing the entire coding region of the CNGB3 gene, eight exons of the GNAT2 gene, and exons 5-7 of the CNGA3 gene was performed. Segregation analysis for the presence and independent inheritance of two mutant alleles was performed in the three families available for study.

Results: All patients showed typical achromatopsia signs and symptoms. Sequencing helped detect causative changes in the CNGB3 gene in all probands. Eight different mutations were detected in the CNGB3 gene, including five novel mutations: two splice site mutations (c.1579-1G>A and c.494-2A>T), one nonsense substitution (c.1194T>G), and two frame-shift mutations (c.393_394delGCinsTCCTGGTGA and c.1366delC). We also found three mutations: one splice site (c.1578+1G>A) and two frame-shift deletions that had been previously described (c.819_826del and c.1148delC). All respective parents were shown to be heterozygous carriers for the mutation detected in their children.

Conclusions: The present study reports five novel mutations in the CNGB3 gene, and thus broadens the spectrum of probably pathogenic mutations associated with ACHM. Together with molecular data, we provide a brief clinical description of the affected individuals.

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Related in: MedlinePlus

ERG of p2. A: Photopic white flash electroretinogram (ERG) shows non-recordable response. B: Scotopic white flash ERG shows normal response. C: Photopic white 30 Hz flicker shows flat response. 1-L indicates the left eye; 2-R indicates the right eye.
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f2: ERG of p2. A: Photopic white flash electroretinogram (ERG) shows non-recordable response. B: Scotopic white flash ERG shows normal response. C: Photopic white 30 Hz flicker shows flat response. 1-L indicates the left eye; 2-R indicates the right eye.

Mentions: Patient p2 was a 12-year-old girl. She initially had nystagmus in early infancy. Photophobia was not present. ERG recordings were consistent with the ACHM pattern: normal scotopic and non-recordable photopic responses. No response was also observed for cone-specific 30 Hz flicker stimulation (Figure 2). The patient displayed normal eye fundus. P2 presented reduced visual acuity 0.08 in the right eye and 0.1 in the left eye. Loss of color discrimination was observed. The patient has a younger brother, but neither her brother nor their parents showed any eye problems.


Five novel CNGB3 gene mutations in Polish patients with achromatopsia.

Wawrocka A, Kohl S, Baumann B, Walczak-Sztulpa J, Wicher K, Skorczyk-Werner A, Krawczynski MR - Mol. Vis. (2014)

ERG of p2. A: Photopic white flash electroretinogram (ERG) shows non-recordable response. B: Scotopic white flash ERG shows normal response. C: Photopic white 30 Hz flicker shows flat response. 1-L indicates the left eye; 2-R indicates the right eye.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4279706&req=5

f2: ERG of p2. A: Photopic white flash electroretinogram (ERG) shows non-recordable response. B: Scotopic white flash ERG shows normal response. C: Photopic white 30 Hz flicker shows flat response. 1-L indicates the left eye; 2-R indicates the right eye.
Mentions: Patient p2 was a 12-year-old girl. She initially had nystagmus in early infancy. Photophobia was not present. ERG recordings were consistent with the ACHM pattern: normal scotopic and non-recordable photopic responses. No response was also observed for cone-specific 30 Hz flicker stimulation (Figure 2). The patient displayed normal eye fundus. P2 presented reduced visual acuity 0.08 in the right eye and 0.1 in the left eye. Loss of color discrimination was observed. The patient has a younger brother, but neither her brother nor their parents showed any eye problems.

Bottom Line: We also found three mutations: one splice site (c.1578+1G>A) and two frame-shift deletions that had been previously described (c.819_826del and c.1148delC).The present study reports five novel mutations in the CNGB3 gene, and thus broadens the spectrum of probably pathogenic mutations associated with ACHM.Together with molecular data, we provide a brief clinical description of the affected individuals.

View Article: PubMed Central - PubMed

Affiliation: Chair and Department of Medical Genetics, Poznan University of Medical Science, Poland.

ABSTRACT

Purpose: To identify the genetic basis of achromatopsia (ACHM) in four patients from four unrelated Polish families.

Methods: In this study, we investigated probands with a clinical diagnosis of ACHM. Ophthalmologic examinations, including visual acuity testing, color vision testing, and full-field electroretinography (ERG), were performed in all patients (with the exception of patient p4, who had no ERG). Direct DNA sequencing encompassing the entire coding region of the CNGB3 gene, eight exons of the GNAT2 gene, and exons 5-7 of the CNGA3 gene was performed. Segregation analysis for the presence and independent inheritance of two mutant alleles was performed in the three families available for study.

Results: All patients showed typical achromatopsia signs and symptoms. Sequencing helped detect causative changes in the CNGB3 gene in all probands. Eight different mutations were detected in the CNGB3 gene, including five novel mutations: two splice site mutations (c.1579-1G>A and c.494-2A>T), one nonsense substitution (c.1194T>G), and two frame-shift mutations (c.393_394delGCinsTCCTGGTGA and c.1366delC). We also found three mutations: one splice site (c.1578+1G>A) and two frame-shift deletions that had been previously described (c.819_826del and c.1148delC). All respective parents were shown to be heterozygous carriers for the mutation detected in their children.

Conclusions: The present study reports five novel mutations in the CNGB3 gene, and thus broadens the spectrum of probably pathogenic mutations associated with ACHM. Together with molecular data, we provide a brief clinical description of the affected individuals.

Show MeSH
Related in: MedlinePlus