Table 1.
Critical review of the current SPG loci curated from the Online Mendelian Inheritance in Man (OMIM) database and a PubMed literature review of “hereditary spastic paraplegia” and each HSP gene and/or loci number.
| Designation | Locus | Gene | Predominant phenotype | Inheritance | OMIM number | Year first reported | Publication count | Family count | Ethnicity | PubMed ID |
|---|---|---|---|---|---|---|---|---|---|---|
| SPG1 | Xq28 | L1CAM | Complicated | X-linked | 303350 | 1986 | 25+ | – | – | – |
| SPG2 | Xq22.2 | PLP1 | Complicated | X-linked | 312920 | 1987 | 20+ | – | – | – |
| SPG3A | 14q22.1 | ATL1 | Pure | AD | 182600 | 1987 | 100+ | – | – | – |
| SPG4 | 2p22.3 | SPAST | Pure | AD | 182601 | 1994 | 200+ | – | – | – |
| SPG5A | 8q12.3 | CYP7B1 | Pure | AR | 270800 | 1994 | 20+ | – | – | – |
| SPG6 | 15q11.2 | NIPA1 | Pure | AD | 600363 | 1995 | 12 | 14 | Irish; Iraqi; Chinese; Japanese; Brazilian; Hungary | 7825577; 14508710; 25341883; 21599812; 21419568; 17928003; 16795073; 16267846; 15643603; 27084228; 25133278; 24075313 |
| SPG7 | 16q24 | SPG7 | Pure or complicated | AR and AD | 607259 | 1998 | 60+ | – | – | – |
| SPG8 | 8q24.13 | WASHC5 | Pure | AD | 603563 | 1999 | 8 | 19 | Caucasian; Brazilian; British; European; Dutch; Chinese; Japanese | 9973294; 10797436; 17160902; 23455931; 29768361; 27957547; 26967522; 25454649 |
| SPG9 | 10q23.3-q24.1 | ALDH18A1 | Complicated | AD | 601162 | 1999 | 4 | 9 | Italian; French; Spanish; Portuguese; Australian; Japanese | 9973297; 26026163; 26297558; 29915212 |
| SPG10 | 12q13.3 | KIF5A | Pure | AD | 604187 | 1999 | 40+ | – | – | – |
| SPG11 | 15q21.1 | SPG11 | Complicated | AR | 604360 | 1999 | 100+ | – | – | – |
| SPG12 | 19q13.32 | RTN2 | Pure | AD | 604805 | 2000 | 3 | 4 | Welsh | 10677333; 22232211; 27165006 |
| SPG13 | 2q33.1 | HSPD1 | Pure | AD | 605280 | 2000 | 3 | 2 | French; Dutch | 10677329; 11898127; 17420924 |
| SPG14 | 3q27-q28 | SPG14 | Complicated | AR | 605229 | 2000 | 1 | 1 | Italian | 10877981 |
| SPG15 | 14q24.1 | ZFYVE26 | Complicated | AR | 270700 | 2001 | 11 | 31 | Arab; Irish; Tunisian; French; Austrian; Italian | 11342696; 17661097; 19438933; 18394578; 19805727; 27217339; 26492578; 24833714; 23733235; 19084844 |
| SPG16 | Xq11.2 | SPG16 | Complicated | X-linked | 300266 | 1997 | 2 | 2 | Japanese; NA | 9254866; 10982474 |
| SPG17 | 11q12.3 | BSCL2 | Complicated | AD | 270685 | 2001 | 9 | 23 | Austrian; English; Brazilian; Italian; Chinese; Portuguese; Korean; Dutch | 11389484; 13680364; 14981520; 29934652; 25487175; 25219579; 18612770; 17486577; 16427281 |
| SPG18 | 8p1123 | ERLIN2 | Complicated | AR and AD | 611225 | 2011 | 6 | 7 | Turkish; Arabian; Northern European; Chinese; Saudi Arabian | 21330303; 23109145; 29528531; 27824013; 23085305; 21796390 |
| SPG19 | 9q | – | Pure | AD | 607152 | 2002 | 1 | 1 | – | 12112072 |
| SPG20 | 13q13.3 | SPART | Complicated | AR | 275900 | 2002 | 7 | 8 | Amish; Omani; Turkish; Filipino; Moroccan | 12134148; 18413476; 20437587; 26003402; 27112432; 28679690; 27539578 |
| SPG21 | 15q22.31 | ACP33 | Complicated | AR | 248900 | 2003 | 2 | 2 | Amish; Japanese | 14564668; 24451228 |
| SPG23 | 1q24-q32 | DSTYK | Complicated | AR | 270750 | 1985 | 3 | 3 | Middle Eastern | 4061404; 14681889; 28157540 |
| SPG24 | 13q14 | – | Pure | AR | 607584 | 2002 | 1 | 1 | Saudi Arabian | 12499481 |
| SPG25 | 6q23-q24.1 | – | Complicated | AR | 608220 | 2002 | 1 | 1 | Italian | 12070243 |
| SPG26 | 12p11.1-q14 | B4GALNT1 | Complicated | AR | 609195 | 2013 | 2 | 7 | Spanish; Portuguese; Tunisian; Bedouin | 23746551; 24283893 |
| SPG27 | 10q22.1-q24.1 | – | Complicated | AR | 609041 | 2004 | 1 | 1 | French Canadian | 15455396 |
| SPG28 | 14q22.1 | DDHD1 | Pure | AR | 609340 | 2005 | 3 | 4 | Moroccan; Turkish; French; Japanese | 23176821; 15786464; 27216551 |
| SPG29 | 1p31.1-p21.1 | – | Complicated | AD | 609727 | 2005 | 1 | 1 | Scottish | 16130112 |
| SPG30 | 2q37.3 | KIF1A | Pure | AR and AD | 610357 | 2011 | 11 | 17 | Palestinian; Algerian; Saudi Arabian; Brazilian; Macedonian; Korean; Sicilian; Chinese | 21487076; 22258533; 25585697; 26410750; 27034427; 28332297; 28362824; 28834584; 28970574; 29159194; 29934652 |
| SPG31 | 2p11 | REEP1 | Pure | AD | 609139 | 2006 | 30+ | – | – | – |
| SPG32 | 14q12-q21 | – | Complicated | AR | 611252 | 2007 | 1 | 1 | Portuguese | 17515546 |
| SPG33 | 10q24.2 | ZFYVE27 | Pure | AD | 610244 | 2006 | 1 | 1 | German | 16826525 |
| SPG34 | Xq24-q25 | – | Pure | X-linked | 300750 | 2008 | 1 | 1 | Brazilian | 18463901 |
| SPG35 | 16q23.1 | FA2H | Complicated | AR | 612319 | 2008 | 14 | 28 | Arab; Omani; Pakistani; Filipino; Chinese; Italian; Turkish | 19068277; 20104589; 20853438; 22965561; 23566484; 23745665; 24359114; 24833714; 26344562; 27217339; 27316240; 28017243; 29376581; 29423566 |
| SPG36 | 12q23-q24 | – | Complicated | AD | 613096 | 2009 | 1 | 1 | German | 19357379 |
| SPG37 | 8p21.1-q13.3 | SPG37 | Pure | AD | 611945 | 2008 | 1 | 1 | French | 17605047 |
| SPG38 | 4p16-p15 | SPG38 | Complicated | AD | 612335 | 2008 | 1 | 1 | Italian | 18401025 |
| SPG39 | 19p13.2 | PNPLA6 | Complicated | AR | 612020 | 2008 | 5 | 10 | Ashkenazi Jewish; German; Japanese; Brazilian | 18313024; 24355708; 23733235; 25631098; 29248984 |
| SPG41 | 11p14.1-p11.2 | SPG41 | Pure | AD | 613364 | 2008 | 1 | 1 | Chinese | 18364116 |
| SPG42 | 3q25.31 | SLC33A1 | Pure | AD | 612539 | 2008 | 1 | 1 | Chinese | 19061983 |
| SPG43 | 19q12 | C19ORF12 | Complicated | AR | 615043 | 2013 | 1 | 1 | Malian | 23857908 |
| SPG44 | 1q42.13 | GJC2 | Complicated | AR | 613206 | 2009 | 1 | 1 | Italian | 19056803 |
| SPG45 | 10q24.3-q25.1 | NT5C2 | Complicated | AR | 613162 | 2009 | 3 | 2 | Turkish; Qatari | 19415352; 24482476; 28327087 |
| SPG46 | 9p13.3 | GBA2 | Complicated | AR | 614409 | 2013 | 6 | 12 | Tunisian; Cypriot; Chinese | 23332916; 23332917; 24252062; 29524657; 27553021; 24337409 |
| SPG47 | 1p13.2 | AP4B1 | Complicated | AR | 614066 | 2011 | 7 | 13 | Israeli; Arab; Turkish; African American | 24781758; 22290197; 24700674; 24781758; 29193663; 27625858; 25693842 |
| SPG48 | 7p22.1 | AP5Z1 | Pure | AR | 613647 | 2010 | 3 | 4 | French; Moroccan | 20613862; 24833714; 26085577 |
| SPG49 | 14q32.31 | TECPR2 | Complicated | AR | 615031 | 2012 | 3 | 3 | Jewish Bukharian | 23176824; 25590979; 27406698 |
| SPG50 | 7q22.1 | AP4M1 | Complicated | AR | 612936 | 2009 | 4 | 5 | Moroccan; Turkish; Greek | 19559397; 21937992; 24700674; 29096665 |
| SPG51 | 15q21.2 | AP4E1 | Complicated | AR | 613744 | 2011 | 4 | 4 | Palestinian; Syrian; Moroccan | 20972249; 21620353; 21937992; 23472171 |
| SPG52 | 14q12 | AP4S1 | Complicated | AR | 614067 | 2011 | 3 | 5 | Syrian; Caucasian; Albanian; Italian | 21620353; 25552650; 27444738 |
| SPG53 | 8p22 | VPS37A | Complicated | AR | 614898 | 2012 | 1 | 2 | Arab | 22717650 |
| SPG54 | 8p11.23 | DDHD2 | Complicated | AR | 615033 | 2012 | 4 | 9 | Dutch; Canadian; Omani; Iranian | 23176823; 23486545; 24482476; 27679996 |
| SPG55 | 12q24.31 | C12ORF65 | Complicated | AR | 615035 | 2012 | 3 | 3 | Japanese; Indian | 24080142; 24198383; 23188110 |
| SPG56 | 4q25 | CYP2U1 | Complicated | AR | 615030 | 2012 | 6 | 9 | Saudi Arabian; Southern Italian; Iranian; Japanese; Turkish; Italian | 23176821; 24337409; 26936192; 27292318; 28725025; 29034544 |
| SPG57 | 3q12.2 | TFG | Complicated | AR | 615658 | 2013 | 5 | 6 | Indian; Italian; Pakistan; Sudanese; British Pakistani; northern Indian | 23479643; 29971521; 28124177; 27601211; 27492651 |
| SPG58 | 17p13.2 | KIF1C | Complicated | AR and AD | – | 2014 | 3 | 6 | Palestinian; Moroccan; Turkish | 24319291; 24482476; 29544888 |
| SPG61 | 16p12.3 | ARL6IP1 | Complicated | AR | 615685 | 2014 | 1 | 1 | – | 24482476 |
| SPG62 | 10q24.3 | ERLIN1 | Complicated | AR | 615681 | 2014 | 1 | 3 | – | 24482476 |
| SPG63 | 1p13.3 | AMPD2 | Complicated | AR | 615686 | 2014 | 1 | 1 | – | 24482476 |
| SPG64 | 10q24.1 | ENTPD1 | Complicated | AR | 615683 | 2014 | 1 | 2 | – | 24482476 |
| SPG72 | 5q31.2 | REEP2 | Pure | AR/AD | 615625 | 2014 | 2 | 3 | French; Portuguese; – | 24388663;28491902 |
| SPG73 | 19q13.33 | CPT1C | Pure | AD | 616282 | 2015 | 1 | 1 | – | 25751282 |
| SPG74 | 1q42.1 | IBA57 | Complicated | AR | 616451 | 2015 | 1 | 1 | Arab | 25609768 |
| SPG75 | 19q13.1 | MAG | Complicated | AR | 616680 | 2014 | 2 | 2 | Pakistani; – | 26179919; 24482476 |
| SPG76 | 11q13.1 | CAPN1 | Complicated | AR | 616907 | 2016 | 4 | 9 | Moroccan; Utah; Irish; Italian | 27153400; 29678961; 27320912; 28566166 |
| SPG77 | 6p25.1 | FARS2 | Pure | AR | 617046 | 2015 | 3 | 4 | Chinese; European | 25851414; 26553276; 29126765 |
| SPG78 | 1p36.1 | ATP13A2 | Complicated | AR | 617225 | 2016 | 2 | 4 | Pakistani; Bulgarian | 27217339; 28137957 |
| SPG79 | 4p13 | UCHL1 | Complicated | AR | 615491 | 2013 | 3 | 3 | Turkish; Norwegian; Indian | 23359680; 28007905; 29735986 |