Table 4.
A Summary of Genetic Variants and Their Severities
| Family No. | Patient No. | ABCA4 Variants | Genotype Class† | |||||
| Allele 1 | Protein | Severity | Allele 2 | Protein | Severity | |||
| F1 | P1 | c.6079C>T | p.(Leu2027Phe) | Intermediate | c.768G>T | p.(Leu257Valfs*17) | Severe | B |
| P2 | ||||||||
| F2 | P3 | c.[2588G>C;5603A>T] | p.[Gly863Ala,Gly863del; Asn1868Ile] | mild1 intermediate2 |
c.[5461–10T>C;5603A>T] | p.[Thr1821Valfs*13, Thr1821Aspfs*6] | Severe | B |
| P4 | ||||||||
| F3 | P5 | c.3617del | p.(Asn1206Metfs*3) | Severe | c.1496G>A | p.(Trp499*) | Severe | A |
| P6 | ||||||||
| F4 | P7 | c.4539+2028C>T | p.[=,Arg1514Leufs*36] | Intermediate | c.6031-6044delins18‡ | p.(Ile2003Leufs*41) | Severe | B |
| P8 | ||||||||
| F5 | P9 | c.6079C>T | p.(Leu2027Phe) | Intermediate | c.4577C>T | p.(Thr1526Met) | Severe | B |
| P10 | ||||||||
| F6 | P11 | c.[5461–10T>C;5603A>T] | p.[,Thr1821Valfs*13, Thr1821Aspfs*6] | Severe | c.4320del | p.(Phe1440Leufs*6) | Severe | A |
| P12 | ||||||||
| F7 | P13 | c.4919G>A | p.(Val1617_Arg1640del, Arg1640Gln) | severe3 | c.4919G>A | P.(Val1617_Arg1640del, Arg1640Gln) | severe3 | A |
| P14 | ||||||||
| F8 | P15 | c.5691G>T | p.(Gln1897His) | Mild | c.768G>T | p.(Leu257Valfs*17) | Severe | C |
| P16 | ||||||||
| F9 | P17 | c.3113C>T | p.(Ala1038Val) | Mild intermediate4 |
c.2564G>A | p.(Trp855*) | Severe | C |
| P18 | ||||||||
| F10 | P19 | c.5537T>A | p.(Ile1846Asn) | Intermediate | c.[240_241del;5908C>T] | p.(Cys81Phefs*17) | Severe | B |
| P20 | ||||||||
| F11 | P21 | c.6079C>T | p.(Leu2027Phe) | Intermediate | c.4577C>T | p.(Thr1526Met) | Severe | B |
| P22 | ||||||||
| P23 | ||||||||
| F12 | P24 | c.3259G>A | p.(Glu1087Lys) | Severe | c.3190G>A | p.(Gly1064Ser) | Severe | A |
| P25 | ||||||||
| F13 | P26 | c.5882G>A | p.(Gly1961Glu) | Mild | c.4320del | p.(Phe1440Leufs*6) | Severe | C |
| P27 | ||||||||
| F14 | P28 | c.1574T>C | p.(Phe525Ser) | Severe | c.1906C>T | p.(Gln636*) | Severe | A |
| P29 | ||||||||
| F15 | P30 | c.5603A>T | p.(Asn1868Ile) | Mild | c.2894A>G | p.(Asn965Ser) | Severe | C |
| P31 | ||||||||
| F16 | P32 | c.1805G>A | p.(Arg602Gln) | Intermediate | c.4577C>T | p.(Thr1526Met) | Severe | B |
| P33 | ||||||||
| F17 | P34 | c.5882G>A | p.(Gly1961Glu) | Mild | c.4577C>T | p.(Thr1526Met) | Severe | C |
| P35 | ||||||||
| F18 | P36 | c.[2588G>C;5603A>T] | p.[Gly863Ala,Gly863del; Asn1868Ile] | Intermediate | c.634C>T | p.(Arg212Cys) | Intermediate | B |
| P37 | ||||||||
| F19 | P38 | c.6089G>A | p.(Arg2030Gln) | Mild | c.3407G>A | p.(Gly1136Glu) | Severe | C |
| P39 | ||||||||
Definition: Class A, severe biallelic mutations. Class B, an allele of intermediate severity in trans with a severe or intermediate allele. Class C, a mild allele in trans with a severe allele.
c.6031_6044delinsAGTATTTAACCAATATTT.
References.
1. Sangermano, R., et al, ABCA4 midigenes reveal the full splice spectrum of all reported noncanonical splice site variants in Stargardt disease. Genome Res, 2018. 28(1): p. 100-110.
2. Fakin, A., et al, The Effect on Retinal Structure and Function of 15 Specific ABCA4 Mutations: A Detailed Examination of 82 Hemizygous Patients. Invest Ophthalmol Vis Sci, 2016. 57(14): p. 5963-5973.
3. Schulz, H.L., et al, Mutation Spectrum of the ABCA4 Gene in 335 Stargardt Disease Patients From a Multicenter German Cohort-Impact of Selected Deep Intronic Variants and Common SNPs. Invest Ophthalmol Vis Sci, 2017. 58(1): p. 394-403.
4. Garces, F., et al, Correlating the Expression and Functional Activity of ABCA4 Disease Variants With the Phenotype of Patients With Stargardt Disease. Invest Ophthalmol Vis Sci, 2018. 59(6): p. 2305-2315.