Table 1.

Genetic causal variants of HSP identified in African populations

Ref	Country	HSP type	Inh	AAO, years	Additional phenotypic features	Gene	HGVS	Gene Variant assessment
								Proband count	Segregation	Pop. freq
Northern Africa
[26]	Tunisia+	SPG5	AR	9–10	WM-HI	CYP7B1	R112* a	1	Yes	No
[14]	Morocco−, Algeria+	SPG7	AR	~ 30  < 10	-	PGN	F284fs/V581delb Q82del	1 1	Yes No	Yes Yes
[9, 15–17, 25]	Algeria±, Morocco+, Tunisia+, Egypt+ Sudan+	SPG11	AR	2–23	± dysarthria/dysphagia; ± Cog; ± scoliosis; ± pes cavus; UL tremor; ± weakness/atrophy UL/LL; ± ataxia; ± epilepsy; ± TCC/WM-HI; ± motor axonopathy	KIAA1840	R2034* c M245fs a,c V2344fs S412L L517fs Q498*a K1190* G2117* A2237fs c.5866 + 1G > Ac	10 5 1 1 1 2 1 1 2 1	Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes	Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
[18, 25]	Tunisia+, Morocco+, Algeria+	SPG15	AR	1– 20	± Cog, ± PBD, pes cavus, ± scoliosis, ± LL atrophy, ± TCC/WM-HI, ± axonopathy	ZFYVE26	S2004T Q493* F683fs R1438* a,c c.5485-1G > A	1 4 2 1 1	Yes Yes Yes Yes Yes	No Yes Yes Yes Yes
[22]	Tunisia+ Algeria+	SPG26	AR	3–19	Cog., ataxia, PNP; WM-HI	B4GALNT1	R300Cc L89fs	1 1	Yes No	Yes Yes
[23]	Morocco+	SPG28	AR	< 1	Cog., WM-HI/BG calcification	DDHD1	R589Q	1	Yes	Yes
[20]	Morocco+	SPG35	AR	4	Cog	FA2H	G46D	1	No	No
[20]	Morocco+	SPG48	AR	< 1	Cog., ataxia	AP5ZI	R206W	1	Yes	No
[21]	Tunisia+	SPG46	AR	2–10	Cog., ataxia, cataracts	GBA2	R630W	1	Yes	Yes
[13]	Morocco+	SPG51	AR	< 1	Cog., PBD	AP4E1	R1105* c,d	1	Yes	Yes
[9]	Sudan	SPG57	AR	< 1.2	± Microcephaly	TFG	R22W c,d	1	Yes	Yes
[9]	Sudan	ARSACS	AR	10–11	± weakness UL/LL; ± ataxia; ± Cog.; SM axonopathy	SACS	W2580*	1	Yes	Yes
[25]	Morocco+	UK	AR	1–5	Ulcero-mutilating neuropathy; SM axonopathy	CCT5	H147R	1	Yes	Yes
[12]	Tunisia+	UK	AR	2	Optic atrophy	RNF170	delEx4_7 d	1	Yes	Yes
[10]	Morocco+	SPG76	AR	20–39	± Dysarthria; ± ataxia; ± pes cavus; scoliosis; PNP	CAPN1	R295P G527*	1 1	Yes Yes	Yes Yes
[11]	Egypt	SPOAN	AR	< 1	Optic atrophy; neuropathy	KLC2	216bpdel 5’UTR a,d	1	UK	Yes
[9]	Sudan	UK	AR	< 1.5	± PBDc	ALS2	C123Y	1	Yes	Yes
[9]	Sudan	SPG3A	AD	1.5–7	± proximal weakness LL	ATL1	F151S	1	Yes	Yes
[25, 27, 28]	Morocco− Tunisia−	SPG4	AD AD S	10–20 12–38 1	± Cog	SPAST	R499C a S404F G442K	> 2 1 1	Yes Yes Yes	Yes Yes Yes
Sub-Saharan Africa
[17]	Kenya+	SPG7	AR	~ 30	Ataxia	PGN	L78 c	1	No	No
[17, 32]	Kenya + Somalia−	SPG11	AR	10–20 ~ 2	Oromandibular dystonia  ± Cog; ± ataxia	KIAA1840	S1923fs c A2237fs	3 1	No No	No No
[29]	Mali+	SPG35	AR	~ 2	dysphagia	FA2H	c.786 + 1G > A a	1	Yes	No
[31]	Mali+	SPG43	AR	7–12	SM neuropathy	C19orf12	A63P a,c	1	No	Yese
[33]	South Africa−	SPG3A	AD	50–60	Cog.; TCC	ATL1	R416C c	1	Yes	Yes
[30]	Mali+	SPG10	AD	10–20	SM neuropathy; axonopathy	KIF5A	K362N	1	Yes	Yes

AAO age of onset, Inh inheritance pattern, AD autosomal dominant, AR autosomal recessive, S sporadic, cog cognitive abnormalities, SM neuropathy refers to sensori-motor polyneuropathy, PNP peripheral neuropathy unspecified, ‘axonopathy’ refers to electrophysiological studies showing axonal loss (either motor and/or sensory); UL upper limb, LL lower limb, PBD pseudobulbar dysarthria reflecting spastic dysarthria and emotional incontinence;—no additional signs other than CMT; ⁺, consanguinity; ⁻, no consanguinity; WM-HI refers to brain MRI findings of white matter hyperintense signal changes; TCC, thinning of corpus callosum; UK, unknown; SPOAN, spastic paraplegia, optic atrophy and neuropathy; HGVS, Human Genome Variation Society protein (p.) level and splice-site coding (c.) level recommendations (version 20.05)

Gene Variant score: Proband count, number of probands investigated by study; Segregation—yes when the pathogenic variant segregation was shown within the family (see methods). Pop. freq., Population frequency- yes when controls in the same population were assessed

^aVariant has been reported in non-African probands/families

^bCompound heterozygous variant

^cPresent in gnomAD v2/v3 (see Additional file: for frequencies)

^dFunctional studies for variant was performed