Table 2 List of identified pathogenic mutations across ABCA4 in STGD1 patients. Genetic analysis of 28 unrelated probands identified ABCA4 mutation genomic position, nucleotide change and zygosity. Representative symbols show the repository servers used to identify the global allele frequency of variants in healthy control population: & The Exome Aggregation Consortium (ExAC); # Trans-Omics for Precision Medicine (TOPMed) Program; * The Genome Aggregation Database (gnomAD). Mutations observed in different location of ABCA4 membrane: Transmembrane domain-1 (TMD-1); Transmembrane domain-2 (TMD-2); Extracellular domain-1 (ECD-1); Extracellular domain-2 (ECD-2); Nucleotide binding domain-1 (NBD-1); Nucleotide binding domain-2 (NBD-2)
ID | Exon/Intron | c.DNA change | Amino acid change | Variant Class | Zygosity | Method | MAF | dbSNP | SIFT | PolyPhen | MetaLR | MT | Domain | Reference |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
2 | 30 | c.C4506A | C1502Ter | Stop Codon | Homozygous | Sanger | 0.00001653& | rs61750149 | – | – | – | DC | ECD2 | [25] |
4 | 14 | c.C1995A | Y665Ter | Stop Codon | Homozygous | Sanger | 0.000008536& | rs757302286 | – | – | – | DC | TMD1 | [26] |
8 | 13 | c.G1819A | G607R | Missense | Homozygous | Sanger | 0.00002502& | rs61749412 | D(0) | PD (1) | D(0.933) | DC | ECD1 | [27] |
9 | 9 | c.G1188A | G396C | Missense | Homozygous | Sanger | N/A | rs866219294 | D(0) | PD(0.995) | D (0.804) | DC | ECD1 | This study |
10 | 12 | c.G1556 T | C519F | Missense | Homozygous | Sanger | – | Novel | D(0) | PD(0.999) | – | DC | ECD1 | This study |
11 | 35 | c.T4956G | Y1652Ter | Stop Codon | Homozygous | Sanger | N/A | rs61750561 | – | – | – | DC | ECD2 | [28] |
13 | 42 | c.G5882A | G1961E | Missense | Homozygous | Sanger | 0.005054& | rs1800553 | D(0) | PD(0.998) | D(0.7) | DC | TMD2 | [29] |
17 | 48 | c.C6658T | Q2220Ter | Stop Codon | Homozygous | Sanger | 0.00000828& | rs61753046 | – | – | – | DC | NBD2 | [30] |
18 | 48 | c.C6658T | Q2220Ter | Stop Codon | Homozygous | Sanger | 0.00000828& | rs61753046 | – | – | – | DC | NBD2 | [30] |
22 | 44 | c.A6095G | H2032R | Missense | Homozygous | Sanger | 0.00000796# | rs1242866408 | D (0) | PD (1) | D (0.924) | DC | NBD2 | [31] |
24 | 19 | c.C2900T | A967V | Missense | Homozygous | Sanger | 0.000003979* | rs1291080436 | D (0) | PD (0.99) | D (0.977) | DC | NBD1 | This study |
25 | 3,42 | c.A217T/c.G5882A | I73F, G1961E | Missense/Missense | Homozygous | ES | 0.005054 | Novel/rs1800553 | D(0)/ D(0) | D(0.92)/PD(0.998) | D(0.983)/D(0.7) | DC | ECD1/NBD2 | This study/[29] |
26 | 19 | c.C2912A | T971A | Missense | Homozygous | ES | 0.000003980* | rs61749450 | D (0) | PD(0.999) | D (0.989) | DC | NBD1 | [6] |
27 | 22 | c.G3323A | A1108H | Missense | Homozygous | ES | 0.00001649& | rs61750121 | – | – | – | DC | NBD1 | [32] |
28 | 19 | c.C2912A | T971A | Missense | Homozygous | ES | 0.0000039804 | rs61749450 | D(0) | PD(0.999) | D (0.989) | DC | NBD1 | [6] |
19 | 14,19,42 | c.C1995A/c.C2912A/c.G5882A | Y665Ter/T971A/G1961E | Stop codon/Missense | Compound Heterozygous | Sanger | 0.000008536/0.000003980/0.005054/ | rs757302286/rs61749450/rs1800553 | −/D(0) | PD(0.998) | −/D(0.7) | DC | TMD1/NBD1/TMD2 | |
20 | 46,48 | c.6355DelC/c.C6658T | Q2220Ter | Del/Missense | Compound Heterozygous | Sanger | 0.00000828 | rs61753046 | −/− | −/− | −/− | DC | NBD2/NBD2 | This study/[30] |
21 | 26,33 | c.C3830T/(c.4774-2A > G) | T1277 M | Missense/Splice variant | Compound Heterozygous | Sanger | 0.0003133& | rs374565343/Novel | D(0.03) | PD(0.835) | D (0.61) | DC | NBD1/ECD2 | This study/[30] |
5 | 14 | c.C1995A | Y665Ter | Stop Codon | Heterozygous | Sanger | 0.000008536 | rs757302286 | – | – | – | DC | TMD1 | [26] |
6 | 26 | c.C3830T | T1277 M | Missense | Heterozygous | Sanger | 0.0003133 | rs374565343 | D(0.03) | PD(0.835) | D (0.61) | DC | NBD1 | [34] |
14 | 40 | c.5710delCAATGinsA | – | Ins/Del | Heterozygous | Sanger | – | Novel | – | – | – | DC | NBD2 | This study |