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A novel PLEC nonsense homozygous mutation (c.7159G?>?T; p.Glu2387*) causes epidermolysis bullosa simplex with muscular dystrophy and diffuse alopecia: a case report.

ABSTRACT: BACKGROUND:Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD; OMIM #226670) is an autosomal recessive disease, characterized mainly by skin blistering at birth or shortly thereafter, progressive muscle weakness, and rarely by alopecia. EBS-MD is caused by mutations in the PLEC gene (OMIM *601282), which encodes plectin, a structural protein expressed in several tissues, including epithelia and muscle. We describe a patient affected with EBS-MD and diffuse alopecia in which we identified a novel pathogenic mutation by PCR amplification of all coding exons and exon-intron boundaries of PLEC gene, followed by bidirectional Sanger sequencing. CASE PRESENTATION:The patient, a 28-year-old female and only child of consanguineous healthy parents, was born after uneventful pregnancy. At 2 days of age, she developed skin and oral mucosal blistering, accompanied by voice hoarseness. On physical examination as an adult, we observed diffuse non-scarring alopecia on the scalp, onychodystrophy (pachyonychia) in all 20 nails, dental decay, mild dysphonia, and severe muscle atrophy mainly affecting the extremities. Neurological examination showed profoundly diminished reflexes. Mutation analysis revealed the patient to be homozygous for the novel PLEC nonsense mutation - c.7159G?>?T (p.Glu2387*) - located in exon 31. Thismutation predicts the lack of expression of the full-length plectin isoform. CONCLUSION:The present case appears to be the second association of EBS-MD with diffuse alopecia, both cases having different mutations involving PLEC exon 31. It remains to be elucidated whether diffuse alopecia results from PLEC mutations and/or from environmental factors.

SUBMITTER: Argyropoulou Z

PROVIDER: S-EPMC5775598 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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A novel PLEC nonsense homozygous mutation (c.7159G > T; p.Glu2387*) causes epidermolysis bullosa simplex with muscular dystrophy and diffuse alopecia: a case report.

Argyropoulou Zoe Z Liu Lu L Ozoemena Linda L Branco Claudia C CC Senra Raquel R Reis-Rego Ângela Â Mota-Vieira Luisa L

BMC dermatology 20180120 1

<h4>Background</h4>Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD; OMIM #226670) is an autosomal recessive disease, characterized mainly by skin blistering at birth or shortly thereafter, progressive muscle weakness, and rarely by alopecia. EBS-MD is caused by mutations in the PLEC gene (OMIM *601282), which encodes plectin, a structural protein expressed in several tissues, including epithelia and muscle. We describe a patient affected with EBS-MD and diffuse alopecia in which we ...[more]

PMID: 29352809

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Project description:ImportanceEpidermolysis bullosa simplex with muscular dystrophy (EBS-MD) is an autosomal recessive disorder caused by pathogenic variants in PLEC1, which encodes plectin. It is characterized by mild mucocutaneous fragility and blistering and muscle weakness. Translational readthrough-inducing drugs, such as repurposed aminoglycoside antibiotics, may represent a valuable therapeutic alternative for untreatable rare diseases caused by nonsense variants.ObjectiveTo evaluate whether systemic gentamicin, at a dose of 7.5 mg/kg/d for 14 consecutive days, is clinically beneficial in a patient with EBS-MD.Design, setting, and participantsA single patient in Madrid, Spain, received 2 treatment courses with gentamicin on July 2019 and February 2020 with a follow-up period of 120 and 150 days, respectively.ResultsIn this case report of a woman in her 30s with EBS-MD, before gentamicin treatment, the patient had mucocutaneous involvement, skeletal and respiratory muscle weakness, and myalgia that negatively affected her quality of life. Outcomes were evaluated with extensive laboratory tests and clinical scales. No nephrotoxic or ototoxic effects were detected after intravenous gentamicin administration. Gentamicin treatment was followed by plectin expression in the skin for at least 5 months. Although minimal changes were noted in skeletal muscle function (as measured by the Hammersmith functional motor scale and its expanded version: 6/40 to 7/40 and from 10/66 to 11/66, respectively) and respiratory musculature (maximal inspiratory and expiratory pressures D0 vs D16, MIP: 2.86 vs 3.63 KPa and MEP: 2.93 vs 4.63 KPa), myalgia disappeared (VAS dropped from 6 to 0), and quality of life improved (EuroQoL-5D-3L pain and anxiety dropped from 2 to 1).Conclusions and relevanceThe findings of this single case report suggest that gentamicin treatment may help suppress PLEC1 premature termination codons and induce plectin expression in EBS-MD primary keratinocytes and skin. Our study suggests that gentamicin may play an important role in treating EBS-MD owing to nonsense variants.

Dataset Information

A novel PLEC nonsense homozygous mutation (c.7159G?>?T; p.Glu2387*) causes epidermolysis bullosa simplex with muscular dystrophy and diffuse alopecia: a case report.

Publications

A novel PLEC nonsense homozygous mutation (c.7159G > T; p.Glu2387*) causes epidermolysis bullosa simplex with muscular dystrophy and diffuse alopecia: a case report.

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