Table 3.
List of all available PNPLA6 variants and associated phenotypes
| Reference | Total case | Eye involved | Phenotype | Variant 1 | Effect 1 | Variant type | Domain 1 | Variant 2 | Effect 2 | Variant type | Domain 2 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Zheng et al, 2018 | 1 | Y | BNS | c.3386G>T | p.G1129V | Missense | Pat | c.3534G>C | p.W1178C | Missense | Pat |
| Tarnutzer et al, 2015 | 1 | Y | BNS | c.288T>G | p.Y96* | Nonsense | - | c.865C>G | p.R289G | Missense | cNMP |
| Tarnutzer et al, 2015 | 1 | Y | BNS | c.343–2A>T | - | Splicing | - | c.4075C>T | p.R1359W | Missense | - |
| Synofzik et al, 2014 | 2 | Y | BNS | c.2212–1G>C | p.V738Qfs*98 | Splicing | cNMP | c.3328G>A | p.V1110M | Missense | Pat |
| Synofzik et al, 2014 | 1 | N | Sporadic ataxia | c.3084_3085insGCCA | p.R1031Qfs*38 | Insertion | Pat | c.3299T>G | p.V1100G | Missense | Pat |
| Synofzik et al, 2014 | 1 | N | HSP | c.787G>A | p.V263I | Missense | cNMP | c.2519G>A | p.G840E | Missense | - |
| Synofzik et al, 2014 | 1 | Y | BNS | c.3134C>T | p.S1045L | Missense | Pat | c.3365C>T | p.P1122L | Missense | Pat |
| Synofzik et al, 2014 | 2 | Y | BNS | c.1732G>T | p.G578W | Missense | cNMP | c.3197T>C | p.F1066S | Missense | Pat |
| Synofzik et al, 2014 | 1 | N | GHS | c.3084_3085insGCCA | p.R1031Qfs*38 | Insertion | Pat | c.4084C>G | p.R1362G | Missense | - |
| Synofzik et al, 2014 | 4 | Y | BNS | c.3173C>T | p.T1058I | Missense | Pat | c.3173C>T | p.T1058I | Missense | Pat |
| Kmoch et al, 2015 | 1 | Y | OMS | c.1571T>C | p.L524P | Missense | cNMP | c.3373G>A | p.D1125N | Missense | Pat |
| Kmoch et al, 2015 | 1 | Y | OMS | c.2116C>T | p.Q706* | Nonsense | cNMP | c.3385G>C | p.G1129R | Missense | Pat |
| Kmoch et al, 2015 | 3 | Y | OMS | c.343–2A>T | - | Splicing | - | c.3373G>A | p.D1125N | Missense | Pat |
| Kmoch et al, 2015 | 1 | Y | LCA | c.3084_3085insGCCA | p.R1031Qfs*38 | Insertion | Pat | c.1076C>T | p.T359I | Missense | - |
| Kmoch et al, 2015 | 1 | Y | OMS | c.3322C>T | p.R1108W | Missense | Pat | c.3385G>C | p.G1129R | Missense | Pat |
| Kmoch et al, 2015 | 1 | Y | OMS | c.1238_1239insC | p.L414Sfs*28 | Insertion | - | c.3385G>C | p.G1129R | Missense | Pat |
| Fogel et al, 2014 | 1 | N | Cerebellar ataxia | c.1484C>T | p.P495L | Missense | - | c.3742C>G | p.Q1248E | Missense | Pat |
| Coutelier et al, 2018 | 1 | N | Spastic ataxia | c.2633G>A | p.G878D | Missense | - | c.2633G>A | p.G878D | Missense | - |
| Coutelier et al, 2018 | 1 | N | Cerebellar ataxia | c.1483C>A | p.P495T | Missense | - | c.1857G>T | p.Q619H | Missense | cNMP |
|
Rainier et al, 2008
Rainier et al, 2011 |
2 | N | MND | c.3178A>G | p.M1060V | Missense | Pat | c.3178A>G | p.M1060V | Missense | Pat |
|
Rainier et al, 2008
Rainier et al, 2011 |
2 | N | MND | c.3084_3085insGCCA | p.R1031Qfs*38 | Insertion | Pat | c.2813G>A | p.R938H | Missense | - |
| Yoon et al, 2013 | 1 | N | Spastic paraplegia | c.1816_1818delinsTA | p.Arg606* | Indels | cNMP | del exons 16–17 | - | Deletion | cNMP |
| Hufnagel et al, 2015 | 2 | Y | OMS/LMS | c.3296G>A | p.R1099Q | Missense | Pat | c.3526G>A | p.G1176S | Missense | Pat |
| Hufnagel et al, 2015 | 1 | Y | OMS/LMS | c.3084_3085insGCCA | p.R1031Qfs*38 | Insertion | Pat | c.3385G>A | p.G1129R | Missense | Pat |
| Hufnagel et al, 2015 | 1 | Y | OMS/LMS | c.1973+2T>G | - | Splicing | cNMP | c.3644T>C | p.V1215A | Missense | Pat |
| Hufnagel et al, 2015 | 1 | Y | OMS/LMS | Dup exons 14–20 | - | Insertion | cNMP | c.3644T>C | p.V1215A | Missense | Pat |
| Hufnagel et al, 2015 | 1 | Y | OMS/LMS | c.3084_3085insGCCA | p.R1031Qfs*38 | Insertion | Pat | c.3385G>A | p.G1129R | Missense | Pat |
| Hufnagel et al, 2015 | 4 | Y | OMS/LMS | c.3084_3085insGCCA | p.R1031Qfs*38 | Insertion | Pat | c.2176G>C | p.G726R | Missense | cNMP |
| D’Amore et al, 2018 | 1 | N | Spastic paraplegia | c.3585C>G | p.D1195E | Missense | Pat | c.2389G>A | p.V797M | Missense | - |
| Teive et al, 2018 | 1 | N | GHS | c.4081C>T | p.R1361* | Missense | - | c.3373G>A | p.D1125N | Missense | Pat |
| Teive et al, 2018 | 1 | Y | BNS | c.3531G>A | p.W1177* | Missense | Pat | c.2441T>C | p.L814P | Missense | - |
| Koh et al, 2015 | 1 | Y | BNS | c.3523_3524insTGTCCG | p.1175_1176insVS | Insertion | Pat | c.2923A>G | p.T975A | Missense | Pat |
| Koh et al, 2015 | 1 | Y | BNS | c.3534G>C | p.W1178C | Missense | Pat | c.3534G>C | p.W1178C | Missense | Pat |
| Deik et al, 2014 | 1 | Y | BNS | c.3134C>T | p.S1045L | Missense | Pat | c.3519C>G | p.S1173R | Missense | Pat |
| Stone et al, 2017 | 1 | Y | Retinal dystrophy | c.3334G>A | p.A1112T | Missense | Pat | c.3547C>T | p.R1183W | Missense | Pat |
| Topaloglu et al, 2014 | 2 | N | GHS | c. 3524C>G | p.S1175C | Missense | Pat | c. 3524C>G | p.S1175C | Missense | Pat |
| Topaloglu et al, 2014 | 2 | Y | BNS | c.1270_1271insG | p.D424Gfs*18 | Insertion | - | c.3439C>T | p.R1147C | Missense | Pat |
| Topaloglu et al, 2014 | 2 | N | GHS | c.2494_2495ins13 | p.G832Vfs*27 | Insertion | - | c.4075C>T | p.R1359W | Missense | - |
| O’Neil et al, 2019 | 1 | Y | BNS | c.3084_3085insGCCA | p.R1031Qfs*38 | Insertion | Pat | c.3548G>A | p.R1183Q | Missense | Pat |
| Patsi et al, 2018 | 1 | Y | OMS | c.3620C>A | p.S1207Y | Missense | Pat | c.3620C>A | p.S1207Y | Missense | Pat |
| #Wiethoff et al, 2017 | 2 | N | Cerebellar ataxia | c.3929A>T/ c.3847G>A | p.D1310V/ p.V1283M |
Missense/ Missense |
-/- | c.3929A>T/ c.3847G>A |
p.D1310V/ p.V1283M |
Missense/ Missense |
-/- |
| Langdahl et al, 2017 | 2 | Y | BNS | c.3084_3085insGCCA | p.R1031Qfs*38 | Insertion | Pat | c.4076G>A | p.R1359Q | Missense | - |
| Salgado et al, 2019 | 4 | N | GHS | c.4081C>T | p.R1361* | Missense | - | c.2404G>C | p.E802Q | Missense | - |
| DeNaro et al, 2018 | 1 | Y | BNS | c.1431T>A | p.C477* | Nonsense | - | c.3034G>A | p.G1012S | Missense | Pat |
| This study | 1 | Y | OMS | c.3846+1G>A | r.3711_3847del | Splicing | Pat | c. 3134C>T | p.S1045L | Missense | Pat |
| This study | 1 | Y | BNS | c.1841+3A>G | r.1841_1842ins1841 +1_1841+185 |
Splicing | cNMP | c. 3547C>T | p.R1183W | Missense | Pat |
| This study | 1 | Y | BNS | c.2212–10A>G | - | Splicing | cNMP | c.3436G>A | p.A1146T | Missense | Pat |
| This study | 1 | Y | BNS | c.2266C>T | p.Q756* | Nonsense | - | c.3436G>A | p.A1146T | Missense | Pat |
| This study | 1 | Y | BNS | c.1238_1239insC | p.L414Sfs*28 | Insertion | - | c.3130A>G | p.T1044A | Missense | Pat |
| Total | 70 |
cNMP: cyclic nucleotide monophosphate (cNMP) binding domain (amino acid interval, 195–316/512–622/635–743); Pat: patatin-like phospholipase domain (amino acid interval, 964–1269); BNS: Boucher–Neuhäuser syndrome; HSP: hereditary spastic paraplegia; GHS: Gordon Holmes syndrome; OMS: Oliver-McFarlane syndrome; LMS: Laurence–Moon syndrome; LCA: Leber congenital amaurosis; MND: motor neuron disease; Y: Yes; N: No
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two homozygous missense variants in this consanguineous family; All the variants are described according to PNPLA6 transcript variant (NM_001166111)