Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort.
The hereditary sensory and autonomic neuropathies (HSAN, also known as the hereditary sensory neuropathies) are a clinically and genetically heterogeneous group of disorders, characterised by a progressive sensory neuropathy often complicated by ulcers and amputations, with variable motor and autonomic involvement. To date, mutations in twelve genes have been identified as causing HSAN. To study the frequency of mutations in these genes and the associated phenotypes, we screened 140 index patients in our inherited neuropathy cohort with a clinical diagnosis of HSAN for mutations in the coding regions of SPTLC1, RAB7, WNK1/HSN2, FAM134B, NTRK1 (TRKA) and NGFB. We identified 25 index patients with mutations in six genes associated with HSAN (SPTLC1, RAB7, WNK1/HSN2, FAM134B, NTRK1 and NGFB); 20 of which appear to be pathogenic giving an overall mutation frequency of 14.3%. Mutations in the known genes for HSAN are rare suggesting that further HSAN genes are yet to be identified. The p.Cys133Trp mutation in SPTLC1 is the most common cause of HSAN in the UK population and should be screened first in all patients with sporadic or autosomal dominant HSAN.
Neurogenetics Unit, National Hospital for Neurology and Neurosurgery, London, UK. gd339@cam.ac.uk
G  L
G
Davidson
S  M
S
Murphy
J  M
J
Polke
M
M
Laura
M  A  M
M
Salih
F
F
Muntoni
J
J
Blake
S
S
Brandner
N
N
Davies
R
R
Horvath
S
S
Price
M
M
Donaghy
M
M
Roberts
N
N
Foulds
G
G
Ramdharry
D
D
Soler
M  P
M
Lunn
H
H
Manji
M  B
M
Davis
H
H
Houlden
M  M
M
Reilly
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D059645:Mutation Rate; D010375:Pedigree; D051102:Serine C-Palmitoyltransferase / Q000235:genetics*; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
C487784:SPTLC1 protein, human; D051102:Serine C-Palmitoyltransferase