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Frequency of ABCA4 mutations in 278 Spanish controls: an insight into the prevalence of autosomal recessive Stargardt disease.

Riveiro-Alvarez R, Aguirre-Lamban J, Lopez-Martinez MA, Trujillo-Tiebas MJ, Cantalapiedra D, Vallespin E, Avila-Fernandez A, Ramos C, Ayuso C - Br J Ophthalmol (2008)

Bottom Line: For the first strategy in control subjects, the p.Arg1129Leu variant was found in two heterozygous individuals, which would mean a carrier frequency for any variant of approximately 6.0% and a calculated arSTGD prevalence of 1:1000.This discrepancy between observed (genotypic) and estimated (phenotypic) prevalence could be due to the existence of non-pathological or low penetrance alleles, which may result in late-onset arSTGD or may be implicated in age-related macular degeneration.This situation should be regarded with special care when genetic counselling is given and further follow-up of these patients should be recommended.

View Article: PubMed Central - PubMed

Affiliation: Fundación Jimenez Diaz, Genetics Department, Madrid, Spain. rriveiro@fjd.es

ABSTRACT

Aim: To determine the carrier frequency of ABCA4 mutations in order to achieve an insight into the prevalence of autosomal recessive Stargardt disease (arSTGD) in the Spanish population.

Methods: arSTGD patients (n = 133) were analysed using ABCR400 microarray and sequencing. Control subjects were analysed by two different strategies: 200 individuals were screened for the p.Arg1129Leu mutation by denaturing-HPLC and sequencing; 78 individuals were tested for variants with the microarray and sequencing.

Results: For the first strategy in control subjects, the p.Arg1129Leu variant was found in two heterozygous individuals, which would mean a carrier frequency for any variant of approximately 6.0% and a calculated arSTGD prevalence of 1:1000. For the second strategy, carrier frequency was 6.4% and therefore an estimated prevalence of the disease of 1:870.

Conclusion: Calculated prevalence of arSTGD based on the ABCA4 carrier frequency could be considerably higher than previous estimation. This discrepancy between observed (genotypic) and estimated (phenotypic) prevalence could be due to the existence of non-pathological or low penetrance alleles, which may result in late-onset arSTGD or may be implicated in age-related macular degeneration. This situation should be regarded with special care when genetic counselling is given and further follow-up of these patients should be recommended.

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Related in: MedlinePlus

The spectrum of ABCA4 disease-associated alleles identified in Spanish Stargardt disease (STGD) patients and relative frequencies. Of these, the prevalent p.Arg1129Leu variant represented the 26% of the mutant alleles.
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bj1-93-10-1359-f02: The spectrum of ABCA4 disease-associated alleles identified in Spanish Stargardt disease (STGD) patients and relative frequencies. Of these, the prevalent p.Arg1129Leu variant represented the 26% of the mutant alleles.

Mentions: Of the 266 arSTGD chromosomes studied, mutations were identified in 161, resulting in a detection rate for the genotyping microarray of 60.5%: two mutant alleles were found in 64/133 patients (48.1%), whereas in 33/133 cases (24.8%) only one allele could be identified. A total of 56 different sequence variants related to the disease were identified, including missense (42), nonsense (four) frameshift (five) and splicing (five) mutations. Furthermore, combinations of variants acting in cis (complex alleles; six double alleles, one triple allele) were also found. Of this spectrum of substitutions, the p.Arg1129Leu (c.3386G>T) allele accounted for 26% of the disease-associated alleles (fig 2). Considering the percentage represented by this variant in patients (26%) and the obtained mutation detection rate (60.5%), this change would represent the 15.7% of all the potential arSTGD associated alleles.


Frequency of ABCA4 mutations in 278 Spanish controls: an insight into the prevalence of autosomal recessive Stargardt disease.

Riveiro-Alvarez R, Aguirre-Lamban J, Lopez-Martinez MA, Trujillo-Tiebas MJ, Cantalapiedra D, Vallespin E, Avila-Fernandez A, Ramos C, Ayuso C - Br J Ophthalmol (2008)

The spectrum of ABCA4 disease-associated alleles identified in Spanish Stargardt disease (STGD) patients and relative frequencies. Of these, the prevalent p.Arg1129Leu variant represented the 26% of the mutant alleles.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2743849&req=5

bj1-93-10-1359-f02: The spectrum of ABCA4 disease-associated alleles identified in Spanish Stargardt disease (STGD) patients and relative frequencies. Of these, the prevalent p.Arg1129Leu variant represented the 26% of the mutant alleles.
Mentions: Of the 266 arSTGD chromosomes studied, mutations were identified in 161, resulting in a detection rate for the genotyping microarray of 60.5%: two mutant alleles were found in 64/133 patients (48.1%), whereas in 33/133 cases (24.8%) only one allele could be identified. A total of 56 different sequence variants related to the disease were identified, including missense (42), nonsense (four) frameshift (five) and splicing (five) mutations. Furthermore, combinations of variants acting in cis (complex alleles; six double alleles, one triple allele) were also found. Of this spectrum of substitutions, the p.Arg1129Leu (c.3386G>T) allele accounted for 26% of the disease-associated alleles (fig 2). Considering the percentage represented by this variant in patients (26%) and the obtained mutation detection rate (60.5%), this change would represent the 15.7% of all the potential arSTGD associated alleles.

Bottom Line: For the first strategy in control subjects, the p.Arg1129Leu variant was found in two heterozygous individuals, which would mean a carrier frequency for any variant of approximately 6.0% and a calculated arSTGD prevalence of 1:1000.This discrepancy between observed (genotypic) and estimated (phenotypic) prevalence could be due to the existence of non-pathological or low penetrance alleles, which may result in late-onset arSTGD or may be implicated in age-related macular degeneration.This situation should be regarded with special care when genetic counselling is given and further follow-up of these patients should be recommended.

View Article: PubMed Central - PubMed

Affiliation: Fundación Jimenez Diaz, Genetics Department, Madrid, Spain. rriveiro@fjd.es

ABSTRACT

Aim: To determine the carrier frequency of ABCA4 mutations in order to achieve an insight into the prevalence of autosomal recessive Stargardt disease (arSTGD) in the Spanish population.

Methods: arSTGD patients (n = 133) were analysed using ABCR400 microarray and sequencing. Control subjects were analysed by two different strategies: 200 individuals were screened for the p.Arg1129Leu mutation by denaturing-HPLC and sequencing; 78 individuals were tested for variants with the microarray and sequencing.

Results: For the first strategy in control subjects, the p.Arg1129Leu variant was found in two heterozygous individuals, which would mean a carrier frequency for any variant of approximately 6.0% and a calculated arSTGD prevalence of 1:1000. For the second strategy, carrier frequency was 6.4% and therefore an estimated prevalence of the disease of 1:870.

Conclusion: Calculated prevalence of arSTGD based on the ABCA4 carrier frequency could be considerably higher than previous estimation. This discrepancy between observed (genotypic) and estimated (phenotypic) prevalence could be due to the existence of non-pathological or low penetrance alleles, which may result in late-onset arSTGD or may be implicated in age-related macular degeneration. This situation should be regarded with special care when genetic counselling is given and further follow-up of these patients should be recommended.

Show MeSH
Related in: MedlinePlus