SEPT9 mutations and a conserved 17q25 sequence in sporadic and hereditary brachial plexus neuropathy.
BACKGROUND
The clinical characteristics of sporadic brachial plexus neuropathy (S-BPN) and hereditary brachial plexus neuropathy (H-BPN) are similar. During attacks, inflammation of the brachial plexus nerves has been identified in both conditions. SEPT9 mutations (Arg88Trp, Ser93Phe, 5'UTR c.-131G>C) occur in some families with H-BPN. These mutations were not found in North American kindreds with H-BPN with a conserved 500-kilobase sequence of DNA at the 17q25 chromosomal region (where SEPT9 localizes) where a founder mutation has been suggested.


OBJECTIVE
To study the 17q25 sequence and SEPT9 in S-BPN (56 individuals) and H-BPN (13 kindreds).


METHODS
Allele analysis at 17q25, SEPT9 DNA sequencing, and messenger RNA analysis from lymphoblast cultures were performed.


RESULTS
A conserved 17q25 sequence was found in 5 of 13 kindreds with H-BPN and 1 individual with S-BPN. This conserved sequence was not found in the family with a SEPT9 mutation (Arg88Trp) or in 182 control subjects. SEPT9 messenger RNA expression levels did not differ between forms of H-BPN and control subjects. No known mutations of SEPT9 were found in S-BPN.


CONCLUSIONS
Rarely, individuals with S-BPN may have the same conserved 17q25 sequence found in many North American kindreds with H-BPN. Individuals with BPN with this conserved sequence do not seem to have SEPT9 mutations or alterations of messenger RNA expression levels in lymphoblast cultures and are predicted to have the most common genetic cause in North America by a founder-effect mutation.
Klein
Christopher J
CJ
Peripheral Neuropathy Research Laboratory, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. klein.christopher@mayo.edu
Wu
Yanhong
Y
Cunningham
Julie M
JM
Windebank
Anthony J
AJ
Dyck
P James B
PJ
Friedenberg
Scott M
SM
Klein
Diane M
DM
Dyck
Peter J
PJ
D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D020516:Brachial Plexus Neuropathies / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D020558:GTP Phosphohydrolases / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009656:North America / Q000208:ethnology; D058112:Septins
D005819:Genetic Markers; D020558:GTP Phosphohydrolases; C474315:SEPTIN9 protein, human; D058112:Septins