PMID: 23755871

Riveiro-Alvarez R, Lopez-Martinez MA, Zernant J, Aguirre-Lamban J, Cantalapiedra D, Avila-Fernandez A, Gimenez A, Lopez-Molina MI, Garcia-Sandoval B, Blanco-Kelly F, Corton M, Tatu S, Fernandez-San Jose P, Trujillo-Tiebas MJ, Ramos C, Allikmets R, Ayuso C
Outcome of ABCA4 disease-associated alleles in autosomal recessive retinal dystrophies: retrospective analysis in 420 Spanish families.
Ophthalmology. 2013 Nov;120(11):2332-7. doi: 10.1016/j.ophtha.2013.04.002. Epub 2013 Jun 4., [PubMed]
Sentences
No. Mutations Sentence Comment
42 ABCA4 p.Arg1129Leu
X
ABCA4 p.Arg1129Leu 23755871:42:98
status: NEW
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ABCA4 p.Arg1129Leu
X
ABCA4 p.Arg1129Leu 23755871:42:199
status: NEW
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ABCA4 p.Arg1129Leu
X
ABCA4 p.Arg1129Leu 23755871:42:432
status: NEW
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Because of the existence of a prevalent disease-associated allele in the Spanish STGD patients, p.Arg1129Leu, 159 arSTGD patients were classified into 4 major categories: (1) those homozygous for p.Arg1129Leu (n &#bc; 8), (2) those compound heterozygous for this mutation (n &#bc; 58), (3) patients with complex alleles on at least 1 chromosome (n &#bc; 10), and (4) those harboring compound heterozygous mutations excluding the p.Arg1129Leu allele (n &#bc; 83). Login to comment
44 ABCA4 p.Arg1129Leu
X
ABCA4 p.Arg1129Leu 23755871:44:38
status: NEW
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Patients who are homozygous for the p.Arg1129Leu allele (i.e., in the first group) always have an arSTGD phenotype at presentation, and the average age at onset of the disease was at the beginning of the third decade of life (20.6), ranging from 12 to 40 years of age. Login to comment
48 ABCA4 p.Arg1129Leu
X
ABCA4 p.Arg1129Leu 23755871:48:110
status: NEW
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Finally, the largest group of patients was compound heterozygous for ABCA4 mutations and did not harbor the p.Arg1129Leu variant. Login to comment
60 ABCA4 p.Arg1129Leu
X
ABCA4 p.Arg1129Leu 23755871:60:44
status: NEW
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In addition, the Spanish founder mutation p.Arg1129Leu was identified in only 3 families with arCRD (MD-0247, MD- 0390, and RP-0532; Table 2, available at http://aaojournal.org). Login to comment
75 ABCA4 p.Arg1129Leu
X
ABCA4 p.Arg1129Leu 23755871:75:21
status: NEW
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The most prevalent p.Arg1129Leu allele, which accounts for 22.4% of the mutant alleles in the Spanish STGD population, is associated mainly with the arSTGD phenotype. Login to comment
78 ABCA4 p.Arg1129Leu
X
ABCA4 p.Arg1129Leu 23755871:78:8
status: NEW
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Thus, p.Arg1129Leu could be considered a relatively moderate allele, and the severity of the phenotype is determined by the second mutation in compound heterozygotes (see below). Login to comment
86 ABCA4 p.Arg1129Leu
X
ABCA4 p.Arg1129Leu 23755871:86:78
status: NEW
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This study has the advantage of the presence of a common missense mutation, p.Arg1129Leu, in the Spanish STGD population that accounts for almost one-fourth of all mutant alleles. Login to comment
87 ABCA4 p.Arg1129Leu
X
ABCA4 p.Arg1129Leu 23755871:87:94
status: NEW
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ABCA4 p.Arg1129Leu
X
ABCA4 p.Arg1129Leu 23755871:87:295
status: NEW
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As seen in Table 1 (available at http://aaojournal.org), 8 patients were homozygous for the p.Arg1129Leu variant and 58 were compound heterozygous, therefore reducing the variability in the patient pool and allowing comparison with other mutations that are found in the same patients with the p.Arg1129Leu variant (which is constant). Login to comment
88 ABCA4 p.Leu541Pro
X
ABCA4 p.Leu541Pro 23755871:88:144
status: NEW
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ABCA4 p.Thr1019Met
X
ABCA4 p.Thr1019Met 23755871:88:170
status: NEW
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ABCA4 p.Arg602Trp
X
ABCA4 p.Arg602Trp 23755871:88:157
status: NEW
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ABCA4 p.His1838Asp
X
ABCA4 p.His1838Asp 23755871:88:202
status: NEW
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ABCA4 p.Leu1940Pro
X
ABCA4 p.Leu1940Pro 23755871:88:184
status: NEW
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Based on our data, the likely severe ABCA4 missense mutations, resulting in an early disease onset and severe disease, include, among others: p.Leu541Pro, p.Arg602Trp, p.Thr1019Met, p.Leu1940Pro, and p.His1838Asp. Login to comment
90 ABCA4 p.Gly1961Glu
X
ABCA4 p.Gly1961Glu 23755871:90:276
status: NEW
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ABCA4 p.Leu541Pro
X
ABCA4 p.Leu541Pro 23755871:90:60
status: NEW
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ABCA4 p.Arg602Trp
X
ABCA4 p.Arg602Trp 23755871:90:76
status: NEW
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ABCA4 p.His1838Asp
X
ABCA4 p.His1838Asp 23755871:90:225
status: NEW
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ABCA4 p.Leu1940Pro
X
ABCA4 p.Leu1940Pro 23755871:90:135
status: NEW
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These results are supported by previous findings that the p.Leu541Pro and p.Arg602Trp variants result in mislocalized protein,22 the p.Leu1940Pro and IVS38e10T/C variants confer much earlier onset of the disease,23 and the p.His1838Asp variant, in a complex allele with the p.Gly1961Glu mutation, results in an early-onset, severe disease.24 Although the above estimates are simplified because they do not take into account environmental factors and genetic variation at other loci in these patients, they serve as a good basis for association with disease onset and disease severity. Login to comment
91 ABCA4 p.Arg18Trp
X
ABCA4 p.Arg18Trp 23755871:91:137
status: NEW
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ABCA4 p.Leu11Pro
X
ABCA4 p.Leu11Pro 23755871:91:125
status: NEW
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ABCA4 p.Ala538Val
X
ABCA4 p.Ala538Val 23755871:91:149
status: NEW
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Almost all disease-associated variants were found in both arSTGD and arCRD phenotypes in our cohort, with the exception of p.Leu11Pro, p.Arg18Trp, p.Ala538Val, and p.Val1973*, which were associated only with CRD. Login to comment