Table 1.
SLC38A8 mutations identified
| Pedigree ID | Patient ID | Gene | Mutation (s) | Zygosity | gnomAD (MAF) | CADD | FATHMM | ACMG | Segregation | Previous literature |
|---|---|---|---|---|---|---|---|---|---|---|
| F1 | F1:II-1 and F1:II-2 | SLC38A8 | c.692G > A:p.(Cys231Tyr) | Compound heterozygous | 1/223 834 | 27.2 | 0.96 | LP | Paternal | Novel |
| SLC38A8 | c.964C > T:p.(Gln322a) | 2/248 656 | 37.0 | 0.97 | P | Maternal | Novel | |||
| F2 | F2:II-1 | SLC38A8 | c.558C > A:p.(Tyr186a) | Compound heterozygous | None | 58.0 | 0.93 | P | Maternal | Novel |
| SLC38A8 | c.1078_1104del:p.(Ala360_Leu368del) | None | 16.3 | 0.99 | LP | Paternal | Novel | |||
| F3 | F3:II-1 | SLC38A8 | c.995dupG:p.(Trp333Metfs*35) | Compound heterozygous | 1/249 760 | 22.9 | 0.72 | P | Paternal | Novel |
| SLC38A8 | c.1214 + 5G > C | None | 14.0 | 0.99 | US | Maternal | Novel | |||
| F4 | F4:II-1 | SLC38A8 | c.855G > C:p.(Leu285Phe) | Compound heterozygous | None | 35.0 | 0.67 | LP | Maternal | Novel |
| SLC38A8 | c.995dupG:p.(Trp333Metfs*35) | 1/249 760 | 16.3 | 0.72 | P | Paternal | Novel | |||
| F5a | F5:II-1 and F5:II-2 | SLC38A8 | c.644G > T:p.(Trp215Leu)c | Compound heterozygous | 10/251 306 | 33.0 | 0.97 | US | NA | Novel |
| SLC38A8 | c.682G > A:p.(Gly228Arg)c | 7/282 722 | 32.0 | 0.99 | US | NA | Novel | |||
| SLC38A8 | c.695A > G:p.(His232Arg) | 1/234 770 | 23.7 | 0.95 | US | Maternal | Novel | |||
| F6 | F6:II-2 | SLC38A8 | c.954-1G > C | Compound heterozygous | None | 23.5 | 0.98 | P | Detected in transd | Novele |
| SLC38A8 | c.995dupG:p.(Trp333Metfs*35) | 1/249 760 | 16.3 | 0.72 | P | Detected in transb | Novel | |||
| F7 | F7:II-3 | SLC38A8 | c.101 T > G:p.Met34Arg | Homozygous | None | 17.2 | 0.99 | LP | Maternal and Paternald | Reportede |
| F8b | F8:II-1 | SLC38A8 | c.632 + 2 T > G | Homozygous | None | 22.9 | 0.99 | P | Maternal and Paternal | Novel |
| F9 | F9:II-1 | SLC38A8 | Exon 1 deletion | Compound heterozygous | None | - | - | P | Maternal | Novel |
| SLC38A8 | c.1126G > A:p.(Gly376Arg) | 2/2 282 530 | 27.1 | 0.96 | LP | Paternal | Novel |
aAdditional variant in F5: FRMD7 (NM_194277.2): c.875 T > C:p.(Leu292Pro) (heterozygous and hemizygous in F5:II-1 and F5:II-2, respectively).
bAdditional variant in F8: TYR (NM_000372): c.1205G > A:p.(Arg402Gln) (homozygous).
cThese two variants were present in cis configuration, confirmed by IGV.
dThese two variants were present in trans configuration, confirmed by IGV.
ePoulter, J.A., Al-Araimi, M., Conte, I. et al. Recessive mutations in SLC38A8 cause foveal hypoplasia and optic nerve misrouting without albinism. Am J Hum Genet. 2013, 1143–1150.
Abbreviations: ACMG = American College of Medical Genetics; CADD = combined annotation dependent depletion; FATHMM = functional analysis through Hidden Markov Models; LP = likely pathogenic; NA = not available; P = pathogenic and US = uncertain significance.