ABCMdb

ABCA4 p.His1838Asp

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Publications

PMID: 22661473 [PubMed] Burke TR et al: "Retinal phenotypes in patients homozygous for the G1961E mutation in the ABCA4 gene."

No. Sentence Comment

87 Two other siblings (patients 7-1 and 7-2), who belonged to a consanguineous Jordanian family, also had the H1838D mutation detected in homozygosity, in addition to being homozygous for the G1961E mutation. Login to comment
91 Summary of Demographic, Clinical, and Functional Data in Patients Homozygous for the G1961E Mutation Patient #, Sex Additional ABCA4 Mutations Onset Age (years) Age at Exam (years) Duration (years) VA Clinical Phenotype ERG Group Silent Choroid Type of Perimetry Scotoma Location OD OS Milder Phenotypes 1, M 19 34 15 20/150 20/100 I I ND MP-1 Central 2, F 20 21 1 20/25 20/40 I I Absent ND ND 3, M T1253M 32 46 14 20/25 20/40 I I Absent GVF Perifoveal 4, F 43 67 24 20/40 20/150 II I ND MP-1 Central 5, F 48 65 17 20/150 20/200 I I ND MP-1 Central 6, F 64 86 22 20/200 20/200 II I Absent GVF Central Severe Phenotypes 7-1, M H1838D (Hom) 4 12 8 20/250 20/250 III III ND GVF Central 7-2, F H1838D (Hom) 7 13 6 20/200 20/200 IV III Peripapillary Ring GVF Central 8-1, F N96K 7 46 39 20/2000 20/2000 III III Peripapillary Ring GVF Central 8-2, M N96K 10 49 39 20/400 20/400 IV ND ND GVF Central 9, F N96K (Hom) 12 59 47 10/400 10/400 IV III ND ND ND 10, M 20 51 31 20/25 20/25 III RP ND GVF Perifoveal Each number identifies distinct families. Login to comment
184 These genetic findings in our patients of Italian origin are in keeping with recent reports of this mutation in Italian populations with STGD1.43 The H1838D mutation has been reported previously in patient 7-1.31 This variant clearly has a profoundly deleterious effect on ABCA4 protein function, at least when present in conjunction with the G1961E in homozygosity, giving rise to a severe, early-onset and complex phenotype in both siblings from a consanguineous family of Jordanian descent. Login to comment
86 Two other siblings (patients 7-1 and 7-2), who belonged to a consanguineous Jordanian family, also had the H1838D mutation detected in homozygosity, in addition to being homozygous for the G1961E mutation. Login to comment
90 Summary of Demographic, Clinical, and Functional Data in Patients Homozygous for the G1961E Mutation Patient #, Sex Additional ABCA4 Mutations Onset Age (years) Age at Exam (years) Duration (years) VA Clinical Phenotype ERG Group Silent Choroid Type of Perimetry Scotoma Location OD OS Milder Phenotypes 1, M 19 34 15 20/150 20/100 I I ND MP-1 Central 2, F 20 21 1 20/25 20/40 I I Absent ND ND 3, M T1253M 32 46 14 20/25 20/40 I I Absent GVF Perifoveal 4, F 43 67 24 20/40 20/150 II I ND MP-1 Central 5, F 48 65 17 20/150 20/200 I I ND MP-1 Central 6, F 64 86 22 20/200 20/200 II I Absent GVF Central Severe Phenotypes 7-1, M H1838D (Hom) 4 12 8 20/250 20/250 III III ND GVF Central 7-2, F H1838D (Hom) 7 13 6 20/200 20/200 IV III Peripapillary Ring GVF Central 8-1, F N96K 7 46 39 20/2000 20/2000 III III Peripapillary Ring GVF Central 8-2, M N96K 10 49 39 20/400 20/400 IV ND ND GVF Central 9, F N96K (Hom) 12 59 47 10/400 10/400 IV III ND ND ND 10, M 20 51 31 20/25 20/25 III RP ND GVF Perifoveal Each number identifies distinct families. Login to comment
183 These genetic findings in our patients of Italian origin are in keeping with recent reports of this mutation in Italian populations with STGD1.43 The H1838D mutation has been reported previously in patient 7-1.31 This variant clearly has a profoundly deleterious effect on ABCA4 protein function, at least when present in conjunction with the G1961E in homozygosity, giving rise to a severe, early-onset and complex phenotype in both siblings from a consanguineous family of Jordanian descent. Login to comment

PMID: 23755871 [PubMed] Riveiro-Alvarez R et al: "Outcome of ABCA4 disease-associated alleles in autosomal recessive retinal dystrophies: retrospective analysis in 420 Spanish families."

No. Sentence Comment

88 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 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

PMID: 23769331 [PubMed] Fujinami K et al: "The clinical effect of homozygous ABCA4 alleles in 18 patients."

No. Sentence Comment

117 The 2 previously reported variants (p.Asn96Lys and p.His1838Asp) in complex with p.Gly1961Glu that were associated with a very severe phenotype were not detected in our patients.12 We observed a particularly late-onset mild disorder, with numerous flecks and foveal sparing, associated with p.Leu2027Phe, suggesting primary disease of the parafoveal RPE with preservation of foveal structure, a "foveal sparing" phenotype. Login to comment