J Clin Neurol.  2015 Oct;11(4):390-394. 10.3988/jcn.2015.11.4.390.

A Novel F45S SOD1 Mutation in Amyotrophic Lateral Sclerosis Coexisting with Bullous Pemphigoid

• Oh SI
• Hong JH
• Choi BW
• Oh KW
• Park CK
• Kwon MJ
• Ki CS
• Ko JY
• Kim SH

• KMID: 2179760
• DOI: http://doi.org/10.3988/jcn.2015.11.4.390

Abstract

BACKGROUND
The coexistence of an autoimmune disease and amyotrophic lateral sclerosis (ALS) has led to the hypothesis that immune-mediated pathological mechanisms are overlapping in the two diseases. We report herein a rare coexistence of bullous pemphigoid (BP) in a novel mutation (F45S) of the gene encoding Cu/Zn superoxide dismutase (SOD1) in an ALS patient, and discuss a role for the SOD1 mutation in this unusual overlap.
CASE REPORT
A 57-year-old male with familial ALS, including vesicles and tense bullae on erythematous bases, was diagnosed with BP. Direct immunofluorescence revealed deposits of C3 and immunoglobulin G in the basement membrane zone. Direct sequencing of SOD1 in the patient revealed a novel mutation (c.137T>C; F45S).
CONCLUSIONS
We report a novel SOD1 mutation in ALS, which was combined with BP. This novel SOD1 mutation could affect the phenotype of a combined autoimmune disease and matrix metalloproteinase-9. There may therefore be common factors linking BP and ALS with the SOD1 mutation.

Keyword

amyotrophic lateral sclerosis; bullous pemphigoid; superoxide dismutase; autoimmunity

MeSH Terms

Amyotrophic Lateral Sclerosis*
Autoimmune Diseases
Autoimmunity
Basement Membrane
Fluorescent Antibody Technique, Direct
Humans
Immunoglobulin G
Male
Matrix Metalloproteinase 9
Middle Aged
Pemphigoid, Bullous*
Phenotype
Superoxide Dismutase
Transcutaneous Electric Nerve Stimulation
Immunoglobulin G
Matrix Metalloproteinase 9
Superoxide Dismutase

Figure

• 

  Fig. 1 A: Pedigree of a family with ALS patients carrying a mutation in SOD1. The available DNA samples are indicated by asterisks (*); the proband (II-2) is marked with an arrow. The filled symbols indicate the affected individuals; the symbols with small dark circles indicate carriers of the SOD1 mutation. B: Sequencing of SOD1 in this family revealed a heterozygous T-to-C substitution at nucleotide position 137, which changes a phenylalanine to serine at codon 45 (c.137T>C; F45S). The patient's youngest sister and daughter had the same mutation, although they remain unaffected.

• 

  Fig. 2 Clinical, histological, and immunofluorescence manifestations. A-C: Bullous pemphigoid in a 59-year-old male with familial amyotrophic lateral sclerosis, as demonstrated by numerous tense blisters arising on a confluent erythematous base (A: left arm; B: left hand; C: right foot). D and E: Microscopic subepidermal blister with an inflammatory cell infiltrate containing eosinophils in the superficial dermis [D: hematoxylin and eosin (H&E) stain, ×40; E: H&E, ×200]. F: Linear deposits of IgG along the basement membrane zone (direct immunofluorescence, ×100). G: IgG bound to the epidermal side of 1-M-NaCl-split skin (indirect immunofluorescence, ×100). IgG: immunoglobulin G.

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