Table 2. Pathogenic or Likely Pathogenic Mutations Identified in 28 Patients With Infantile Nystagmus Syndrome.
| Patient No. | Initial Diagnosis | Gene | Zygosity | Mutations | Segregation Analysis | ExAC (MAF) |
In Silico Prediction (FATHMM) | Previous Literature |
Accession ID for Transcripta |
|---|---|---|---|---|---|---|---|---|---|
| 1 | LCA | GUCY2D | Compound; heterozygous | c.1978C>T: p.Arg660Ter; c.3038G>A: p.Gly1013Glu | Paternal; maternal | 0.0002; none |
NA; D (–2.12) |
Reference17; novel |
NM_000180.3 |
| 2b | LCA | GUCY2D | Compound; heterozygous | c.1991A>C: p.His664Pro; c.2649delT: p.Phe883LeufsTer13 | Paternal; maternal | None; none |
D (–1.86); NA |
Novel; novel |
NM_000180.3 |
| 3 | LCA | GUCY2D | Homozygous | c.2649delT: p.Phe883LeufsTer13 | NA | None | NA | Novel | NM_000180.3 |
| 4b | LCA | GUCY2D | Compound; heterozygous | c.2649delT: p.Phe883LeufsTer13; c.3038G>A: p.Gly1013Glu | Paternal; maternal | None; none |
NA; D (–2.12) |
Novel; novel |
NM_000180.3 |
| 5 | LCA | GUCY2D | Compound; heterozygous | c.2818C>T: p.Arg940Trp; c.3038G>A: p.Gly1013Glu | Paternal; maternal | 0.0000083; none |
D (–1.55); D (–2.12) |
Novel; novel |
NM_000180.3 |
| 6b | LCA | NMNAT1 | Compound; heterozygous | c.196C>T: p.Arg66Trp; c.709C>T: p.Arg237Cys | Maternal; paternal | 0.00013; 0.000074 |
D (–6.60); D (–4.67) |
References18,19; references18,19,20 |
NM_022787.3 |
| 7b | LCA | NMNAT1 | Compound; heterozygous | c.196C>T: p.Arg66Trp; c.709C>T: p.Arg237Cys | Maternal; paternal | 0.00013; 0.000074 |
D (–6.60); D (–4.67) |
References18,19; references18,19,20 |
NM_022787.3 |
| 8 | LCA | NMNAT1 | Compound; heterozygous | c.709C>T: p.Arg237Cys; exon 4, 5 deletion |
Paternal; maternal | 0.000074; none |
D (–4.67); NA |
References18,19,20; reference21 |
NM_022787.3 |
| 9 | LCA | RPGRIP1 | Compound; heterozygous | c.2302C>T: p.Arg768Ter; c.3565_3571del: pArg1189GlyfsTer7 | Paternal; maternal | 0.000039; 0.000017 |
NA; NA |
Novel; reference22 |
NM_020366.3 |
| 10 | IIN | RPGRIP1 | Homozygous | c.3565_3571del: p.Arg1189GlyfsTer7 | NA | 0.000017 | NA | Reference22 | NM_020366.3 |
| 11 | LCA | CEP290 | Compound; heterozygous | c.1666delA: p.Ile556PhefsTer17; c.6012-12T>A | Maternal; paternal | 0.0142; 0.000025 |
NA; 0.25177 |
References23,24; references24,25 |
NM_025114.3 |
| 12b | LCA | CEP290 | Compound; heterozygous | c.-1G>A; c.6012-12T>A | Paternal; maternal | 0.0000089; 0.000025 |
0.90875; 0.25177 |
Novel; references24,25 |
NM_025114.3 |
| 13 | IIN | CRB1 | Compound; heterozygous | c.1208C>G: p.Ser403Ter; c.1576C>T: p.Arg526Ter | Paternal; maternal | None; none |
NA; NA | Reference26; reference23 |
NM_201253.2 |
| 14b | LCA | CRX | Heterozygous | c.442delG: p.Gly148AlafsTer39 | De novo | None | NA | Novel | NM_000554.5 |
| 15 | LCA | WDR19 | Homozygous | c.3533G>A: p.Arg1178Gln | NA | 0.00058 | Tolerated; (–0.91) |
Reference27 | NM_025132.3 |
| 16 | OA | GPR143 | Hemizygous | c.514G>C: p.Gly172Arg | NA | None | D (–6.09) | Novel | NM_000273.2 |
| 17 | IIN | GPR143 | Hemizygous | c.659-3C>G | NA | None | 0.90355 | Novel | NM_000273.2 |
| 18 | OA | GPR143 | Hemizygous | Exon 2, 3 deletion | NA | None | NA | Reference28 | NM_000273.2 |
| 19 | OA | GPR143 | Hemizygous | Exon 2, 3 deletion | NA | None | NA | Reference28 | NM_000273.2 |
| 20 | IIN | PAX6 | Heterozygous | c.113G>C: p.Arg38Pro | NA | None | D (–6.36) | Novel | NM_000280.4 |
| 21 | PAX6 | PAX6 | Heterozygous | c.622C>T: p.Arg208Trp | NA | 0.0000082 | D (–3.83) | References29,30 | NM_000280.4 |
| 22 | PAX6 | PAX6 | Heterozygous | c.782G>T: p.Arg261Leu | NA | None | D (–4.43) | Novel | NM_000280.4 |
| 23 | IIN | PAX6 | Heterozygous | c.1088C>A: p.Ser363Ter | NA | None | NA | Novel | NM_000280.4 |
| 24 | ACHM | CNGA3 | Compound; heterozygous | c.1262delA: p.Lys421SerfsTer44; c.1642G>A: p.Gly548Arg | Paternal; maternal | None; 0.000025 |
NA; D (–6.35) |
Novel; novel |
NM_001298.2 |
| 25 | ACHM | CNGB3 | Homozygous | c.1928 + 2T>C | NA | None | 0.99601 | Novel | NM_019198.4 |
| 26 | IIN | FRMD7 | Heterozygous | c.901T>C: p.Tyr301His | NA | None | D (–4.63) | Novel | NM_194277.2 |
| 27 | IIN | FRMD7 | Hemizygous | c.910C>T: p.Arg304Ter | NA | None | NA | References18,31,32 | NM_194277.2 |
| 28 | IIN | CACNA1F | Hemizygous | c.342delC: p.Phe115SerfsTer22 | Maternal | None | NA | Novel | NM_005183.2 |
Abbreviations: ACHM, achromatopsia; D, damaging; ExAC, Exome Aggregation Consortium; FATHMM, functional analysis through hidden Markov models; IIN, idiopathic infantile nystagmus; LCA, Leber congenital amaurosis; MAF, minor allele frequency; NA, not available; OA, ocular albinism.
a
NM numbers were the accession identification numbers for longest transcript of the gene provided by Ensembl.
b
Previously reported with different next-generation sequencing methods using clinical exome sequencing (TruSight One sequencing panel).33