Duplication within the SEPT9 gene associated with a founder effect in North American families with hereditary neuralgic amyotrophy

Megan L. Landsverk, Elizabeth K. Ruzzo, Heather C. Mefford, Karen Buysse, Jillian G. Buchan, Evan E. Eichler, Elizabeth M. Petty, Esther A. Peterson, Dana M. Knutzen, Karen Barnett, Martin R. Farlow, Judy Caress, Gareth J. Parry, Dianna Quan, Kathy L. Gardner, Ming Hong, Zachary Simmons, Thomas D. Bird, Phillip F. Chance, Mark C. Hannibal

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder associated with recurrent episodes of focal neuropathy primarily affecting the brachial plexus. Point mutations in the SEPT9 gene have been previously identified as the molecular basis of HNA in some pedigrees. However in many families, including those from North America demonstrating a genetic founder haplotype, no sequence mutations have been detected. We report an intragenic 38 Kb SEPT9 duplication that is linked to HNA in 12 North American families that share the common founder haplotype. Analysis of the breakpoints showed that the duplication is identical in all pedigrees, and molecular analysis revealed that the duplication includes the 645 bp exon in which previous HNA mutations were found. The SEPT9 transcript variants that span this duplication contain two in-frame repeats of this exon, and immunoblotting demonstrates larger molecular weight SEPT9 protein isoforms. This exon also encodes for a majority of the SEPT9 N-terminal proline rich region suggesting that this region plays a role in the pathogenesis of HNA.

Original languageEnglish (US)
Pages (from-to)1200-1208
Number of pages9
JournalHuman Molecular Genetics
Volume18
Issue number7
DOIs
StatePublished - Apr 1 2009

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Brachial Plexus Neuritis
Founder Effect
Exons
Genes
Pedigree
Haplotypes
Mutation
Brachial Plexus
North America
Point Mutation
Immunoblotting
Proline
Protein Isoforms
Molecular Weight

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Landsverk, M. L., Ruzzo, E. K., Mefford, H. C., Buysse, K., Buchan, J. G., Eichler, E. E., ... Hannibal, M. C. (2009). Duplication within the SEPT9 gene associated with a founder effect in North American families with hereditary neuralgic amyotrophy. Human Molecular Genetics, 18(7), 1200-1208. https://doi.org/10.1093/hmg/ddp014
Landsverk, Megan L. ; Ruzzo, Elizabeth K. ; Mefford, Heather C. ; Buysse, Karen ; Buchan, Jillian G. ; Eichler, Evan E. ; Petty, Elizabeth M. ; Peterson, Esther A. ; Knutzen, Dana M. ; Barnett, Karen ; Farlow, Martin R. ; Caress, Judy ; Parry, Gareth J. ; Quan, Dianna ; Gardner, Kathy L. ; Hong, Ming ; Simmons, Zachary ; Bird, Thomas D. ; Chance, Phillip F. ; Hannibal, Mark C. / Duplication within the SEPT9 gene associated with a founder effect in North American families with hereditary neuralgic amyotrophy. In: Human Molecular Genetics. 2009 ; Vol. 18, No. 7. pp. 1200-1208.
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title = "Duplication within the SEPT9 gene associated with a founder effect in North American families with hereditary neuralgic amyotrophy",
abstract = "Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder associated with recurrent episodes of focal neuropathy primarily affecting the brachial plexus. Point mutations in the SEPT9 gene have been previously identified as the molecular basis of HNA in some pedigrees. However in many families, including those from North America demonstrating a genetic founder haplotype, no sequence mutations have been detected. We report an intragenic 38 Kb SEPT9 duplication that is linked to HNA in 12 North American families that share the common founder haplotype. Analysis of the breakpoints showed that the duplication is identical in all pedigrees, and molecular analysis revealed that the duplication includes the 645 bp exon in which previous HNA mutations were found. The SEPT9 transcript variants that span this duplication contain two in-frame repeats of this exon, and immunoblotting demonstrates larger molecular weight SEPT9 protein isoforms. This exon also encodes for a majority of the SEPT9 N-terminal proline rich region suggesting that this region plays a role in the pathogenesis of HNA.",
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Landsverk, ML, Ruzzo, EK, Mefford, HC, Buysse, K, Buchan, JG, Eichler, EE, Petty, EM, Peterson, EA, Knutzen, DM, Barnett, K, Farlow, MR, Caress, J, Parry, GJ, Quan, D, Gardner, KL, Hong, M, Simmons, Z, Bird, TD, Chance, PF & Hannibal, MC 2009, 'Duplication within the SEPT9 gene associated with a founder effect in North American families with hereditary neuralgic amyotrophy', Human Molecular Genetics, vol. 18, no. 7, pp. 1200-1208. https://doi.org/10.1093/hmg/ddp014

Duplication within the SEPT9 gene associated with a founder effect in North American families with hereditary neuralgic amyotrophy. / Landsverk, Megan L.; Ruzzo, Elizabeth K.; Mefford, Heather C.; Buysse, Karen; Buchan, Jillian G.; Eichler, Evan E.; Petty, Elizabeth M.; Peterson, Esther A.; Knutzen, Dana M.; Barnett, Karen; Farlow, Martin R.; Caress, Judy; Parry, Gareth J.; Quan, Dianna; Gardner, Kathy L.; Hong, Ming; Simmons, Zachary; Bird, Thomas D.; Chance, Phillip F.; Hannibal, Mark C.

In: Human Molecular Genetics, Vol. 18, No. 7, 01.04.2009, p. 1200-1208.

Research output: Contribution to journalArticle

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T1 - Duplication within the SEPT9 gene associated with a founder effect in North American families with hereditary neuralgic amyotrophy

AU - Landsverk, Megan L.

AU - Ruzzo, Elizabeth K.

AU - Mefford, Heather C.

AU - Buysse, Karen

AU - Buchan, Jillian G.

AU - Eichler, Evan E.

AU - Petty, Elizabeth M.

AU - Peterson, Esther A.

AU - Knutzen, Dana M.

AU - Barnett, Karen

AU - Farlow, Martin R.

AU - Caress, Judy

AU - Parry, Gareth J.

AU - Quan, Dianna

AU - Gardner, Kathy L.

AU - Hong, Ming

AU - Simmons, Zachary

AU - Bird, Thomas D.

AU - Chance, Phillip F.

AU - Hannibal, Mark C.

PY - 2009/4/1

Y1 - 2009/4/1

N2 - Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder associated with recurrent episodes of focal neuropathy primarily affecting the brachial plexus. Point mutations in the SEPT9 gene have been previously identified as the molecular basis of HNA in some pedigrees. However in many families, including those from North America demonstrating a genetic founder haplotype, no sequence mutations have been detected. We report an intragenic 38 Kb SEPT9 duplication that is linked to HNA in 12 North American families that share the common founder haplotype. Analysis of the breakpoints showed that the duplication is identical in all pedigrees, and molecular analysis revealed that the duplication includes the 645 bp exon in which previous HNA mutations were found. The SEPT9 transcript variants that span this duplication contain two in-frame repeats of this exon, and immunoblotting demonstrates larger molecular weight SEPT9 protein isoforms. This exon also encodes for a majority of the SEPT9 N-terminal proline rich region suggesting that this region plays a role in the pathogenesis of HNA.

AB - Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder associated with recurrent episodes of focal neuropathy primarily affecting the brachial plexus. Point mutations in the SEPT9 gene have been previously identified as the molecular basis of HNA in some pedigrees. However in many families, including those from North America demonstrating a genetic founder haplotype, no sequence mutations have been detected. We report an intragenic 38 Kb SEPT9 duplication that is linked to HNA in 12 North American families that share the common founder haplotype. Analysis of the breakpoints showed that the duplication is identical in all pedigrees, and molecular analysis revealed that the duplication includes the 645 bp exon in which previous HNA mutations were found. The SEPT9 transcript variants that span this duplication contain two in-frame repeats of this exon, and immunoblotting demonstrates larger molecular weight SEPT9 protein isoforms. This exon also encodes for a majority of the SEPT9 N-terminal proline rich region suggesting that this region plays a role in the pathogenesis of HNA.

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