Plectin deficiency leads to both muscular dystrophy and pyloric atresia in epidermolysis bullosa simplex.

Abstract

Plectin is a cytoskeletal linker protein which has a long central rod and N- and C-terminal globular domains. Mutations in the gene encoding plectin (PLEC) cause two distinct autosomal recessive subtypes of epidermolysis bullosa: EB simplex (EBS) with muscular dystrophy (EBS-MD), and EBS with pyloric atresia (EBS-PA). Previous studies have demonstrated that loss of full-length plectin with residual expression of the rodless isoform leads to EBS-MD, whereas complete loss or marked attenuation of expression of full-length and rodless plectin underlies the more severe EBS-PA phenotype. However, muscular dystrophy has never been identified in EBS-PA, not even in the severe form of the disease. Here, we report the first case of EBS associated with both pyloric atresia and muscular dystrophy. Both of the premature termination codon-causing mutations of the proband are located within exon 32, the last exon of PLEC. Immunofluorescence and immunoblot analysis of skin samples and cultured fibroblasts from the proband revealed truncated plectin protein expression in low amounts. This study demonstrates that plectin deficiency can indeed lead to both muscular dystrophy and pyloric atresia in an individual EBS patient.

• Authors: Ken Natsuga, Wataru Nishie, Satoru Shinkuma, Ken Arita, Hideki Nakamura, Makiko Ohyama, Hitoshi Osaka, Takeshi Kambara, Yoshiaki Hirako, Hiroshi Shimizu
• Journal: Human mutation (Hum Mutat) Vol. 31 Issue 10 Pg. E1687-98 (Oct 2010) ISSN: 1098-1004 [Electronic] United States
• PMID: 20665883 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 Wiley-Liss, Inc.

Chemical References

• PLEC protein, human
• Plectin

Topics

• Base Sequence
• Cells, Cultured
• Digestive System Abnormalities (complications, genetics)
• Epidermolysis Bullosa Simplex (complications, genetics, physiopathology)
• Exons (genetics)
• Fatal Outcome
• Female
• Fibroblasts (metabolism)
• Fluorescent Antibody Technique
• Genotype
• Humans
• Immunoblotting
• Infant, Newborn
• Male
• Molecular Sequence Data
• Muscular Dystrophies (complications, genetics)
• Mutation
• Phenotype
• Plectin (chemistry, deficiency, genetics, metabolism)
• Pylorus (abnormalities)
• Skin (metabolism)