Skip to main content

Table 1 Genetic causal variants of HSP identified in African populations

From: A review of the genetic spectrum of hereditary spastic paraplegias, inherited neuropathies and spinal muscular atrophies in Africans

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, 15,16,17, 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

  1. 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)
  2. 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
  3. aVariant has been reported in non-African probands/families
  4. bCompound heterozygous variant
  5. cPresent in gnomAD v2/v3 (see Additional file: for frequencies)
  6. dFunctional studies for variant was performed