Table 7:
HPS5 Pathogenic Gene Variants Associated with Hermansky-Pudlak Syndrome Type 5 (HPS-5)
| No | mRNA NM_181507.1 | Amino Acid NP_852608.1 | Exon/Intron | Variant Type 1 | Ethnic Background 2 | References and Footnotes |
|---|---|---|---|---|---|---|
| 1 | c.219G>A | p.Arg73Arg 3 | Exon 3 | Splice site | Turkish | (Lasseaux et al., 2018; Michaud et al., 2017) 3,4 |
| 2 | c.285–10A>G | IVS4–10A>G | Intron 4 | Splice site | Turkish | (Stephen et al., 2017) 4 |
| 3 | c.302_305delTTTG | p.Val101Glyfs*3 | Exon 5 | Indel | Cuban, Venezuelan | (Carmona-Rivera, Golas, et al., 2011) |
| 4 | c.434G>A | p.Gly145Glu 5 | Exon 5 | Missense | German, Irish, Welsh | (Nazarian et al., 2008) |
| 5 | c.719G>C | p.Arg240Pro | Exon 7 | Missense | African-French | (Lasseaux et al., 2018; Michaud et al., 2017) 4 |
| 6 | c.803delC 6 | p.Pro268Leufs*4 | Exon 7 | Frameshift | - | (Ringeisen et al., 2013) 6 |
| 7 | del 1.4-kb 7,8 | - | Exon 7 | Indel | African-French | (Michaud et al., 2017) 4,7 |
| 8 | c.814_818delATTAC | p.Ile272Serfs*8 | Exon 7 | Indel | - | (Lasseaux et al., 2018) 4 |
| 9 | c.818_822delCTCTC | p.Thr273Lysfs*7 | Exon 7 | Indel | French | (Michaud et al., 2017) 4 |
| 10 | c.879dupC | p.Lys294Glnfs*6 | Exon 8 | Frameshift | English, Irish | (Huizing et al., 2004) |
| 11 | c.888dupA | p.His297Thrfs*3 | Exon 8 | Frameshift | Turkish | (Korswagen et al., 2008) |
| 12 | c.1417C>T | p.Gln473* | Exon12 | Nonsense | Turkish | (Lasseaux et al., 2018; Michaud et al., 2017) 4 |
| 13 | c.1423delC | p.Leu475Serfs*37 | Exon 12 | Frameshift | Mexican | (Carmona-Rivera, Golas, et al., 2011) |
| 14 | c.1618C>T | p.Gln540* | Exon 13 | Nonsense | Arabic | (Khan et al., 2016) 4 |
| 15 | c.1634+1G>A | IVS13+1G>A | Intron13 | Splice site | Cuban, Venezuelan | (Carmona-Rivera, Golas, et al., 2011) |
| 16 | c.1871T>G | p.Leu624Arg 9 | Exon 16 | Missense | Swiss | (Huizing et al., 2004; Lasseaux et al., 2018; Michaud et al., 2017) 4,9 |
| 17 | c.1900delG | p.Glu634Serfs*3 | Exon 16 | Frameshift | - | (Lasseaux et al., 2018; Michaud et al., 2017) 4 |
| 18 | c.1960A>T | p.Lys654* | Exon 16 | Nonsense | English, German, Scottish | (Botero et al., 2018) 4 |
| 19 | c.2026_2029delGTTA | p.Val676Metfs*8 | Exon 16 | Indel | Turkish | (Zhang et al., 2003) |
| 20 | c.2219T>C | p.Leu740Ser | Exon 16 | Missense | - | (Lasseaux et al., 2018; Michaud et al., 2017) 4 |
| 21 | c.2234T>C | p.Leu745Ser | Exon 16 | Missense | Chinese | (Wei et al., 2016) 4,10 |
| 22 | c.2593C>T | p.Arg865* | Exon 18 | Nonsense | Dutch, English, Irish, Swedish | (Huizing et al., 2004) |
| 23 | c.2624delT | p.Leu875Cysfs*20 | Exon 18 | Frameshift | Dutch, English, Irish, Swedish | (Huizing et al., 2004) |
| 24 | c.2750_2751delAG | p.Glu917Valfs*14 | Exon19 | Indel | French | (Lasseaux et al., 2018; Michaud et al., 2017) 4 |
| 25 | c.2928_2929dupGA | p.Thr977Argfs*15 | Exon 20 | Indel | English, Irish | (Huizing et al., 2004) |
| 26 | c.2974_2977delCTCT | p.Leu992Valfs*17 | Exon 21 | Indel | - | (Lasseaux et al., 2018) 4 |
| 27 | c.2979_2982delTTTG | p.Cys993Trpfs*16 | Exon 21 | Indel | French | (Michaud et al., 2017) 4 |
| 28 | c.3058+3A>G | IVS21+3A>G | Intron 21 | Splice site | Turkish | (Lasseaux et al., 2018; Michaud et al., 2017) 4 |
| 29 | c.3096_3098delCCT | p.Leu1033del | Exon 22 | Indel | French | (Michaud et al., 2017) 4 |
| - 8 | c.3293C>T | p.Thr1098Ile 9 | Exon 22 | Missense | Swiss | (Huizing et al., 2004) 9 |
| 30 | c.3346A>G | p.Met1116Val | Exon 23 | Missense | Chinese | (Wei et al., 2016) 4,10 |
| 31 | del 1.5-kb 8 | - | - | Indel | - | (Lasseaux et al., 2018) 4 |
When deletion/insertion is 1 nucleotide it is named Frame shift, when larger it is named Indel.
Extracted from literature reference. ‘-‘ = unreported.
This (silent) HPS5 variant c.219G>A; p.Arg73Arg occurs at the exon3/intron 3 splice site junction and is predicted to affect splicing (Supplemental Table S2).
At least one of the reported cases with this variant was identified by next generation sequencing.
Gray highlight: missense variant. Gray highlight: missense variant. See Supplemental Table S1 for pathogenicity description.
This variant was previously described as c.1081delC (Ringeisen et al., 2013).
Described as Chr11:18327845 to Chr11:18329253 (Michaud et al., 2017).
The nomenclature of these HPS6 variants are included in this Table as reported, see reference for each specific variant for more details.
Two siblings were homozygous for 2 missense HPS5 variants (hemizygosity was excluded): p.Leu624Arg and p.Thr1098Ile (Huizing et al., 2004). The high MAF and low pathogenicity prediction (Supplemental Table S1) classifies p.Thr1098Ile as a benign SNP. Variant p.Leu624Arg classifies as a likely pathogenic missense and is also identified in other HPS-5 individuals in trans with a pathogenic variant (Lasseaux et al., 2018; Michaud et al., 2017).
These variants were originally reported as c.1892T>C and c.3004A>G, using NM_007216 (HPS5 mRNA Variant 2) nomenclature. For this report, the nomenclature of these variants was converted to NM_181507.1 (HPS5 mRNA Variant 1).