Novel compound heterozygous mutations in the PLEC gene in a neonate with epidermolysis bullosa simplex with pyloric atresia - PubMed (original) (raw)

. 2023 Feb;50(2):239-244.

doi: 10.1111/1346-8138.16553. Epub 2022 Aug 23.

Kazumasa Takahashi 1, Naoki Ohta 1, Seigo Okada 1, Sasagu Kimura 1, Shuichiro Yasuno 2, Susumu Murata 3, Shunsaku Katsura 4, Naoyuki Yamada 5, Koji Shiraishi 6, Junko Tsuda 7, Shunsuke Miyai 8, Hiroki Kurahashi 8, Shunji Hasegawa 1, Yutaka Shimomura 2

Affiliations

• PMID: 35996939
• DOI: 10.1111/1346-8138.16553

Novel compound heterozygous mutations in the PLEC gene in a neonate with epidermolysis bullosa simplex with pyloric atresia

Hidenobu Kaneyasu et al. J Dermatol. 2023 Feb.

Abstract

Epidermolysis bullosa (EB) is a heterogeneous group of inherited disorders characterized by the blistering of the skin and mucous membranes. Although the molecular basis of EB has been significantly elucidated, the precise phenotypes of the lethal types of EB have not been completely characterized. Herein, we report a severe case of EB with pyloric atresia (PA). The patient was a Japanese boy who not only had skin lesions but also various complications such as PA, dysphagia, hypotonia, infectious keratitis with corneal ulcer, obstructive uropathy and protein-losing enteropathy. Genetic analysis led to the identification of two novel compound heterozygous mutations in the last exon of the plectin (PLEC) gene. Based on this finding, EB simplex with PA was diagnosed. Immunostaining with anti-plectin antibodies revealed truncated plectin proteins lacking the C-terminus in the patient's skin. We also conducted a prenatal diagnosis in subsequent pregnancy. Our report further highlights the crucial role of plectin in many organs and provides valuable information regarding the phenotypes resulting from mutations in the PLEC gene.

Keywords: PLEC; epidermolysis bullosa; plectin; pyloric atresia.

© 2022 Japanese Dermatological Association.

PubMed Disclaimer

Similar articles

• Plectin deficiency leads to both muscular dystrophy and pyloric atresia in epidermolysis bullosa simplex.
  Natsuga K, Nishie W, Shinkuma S, Arita K, Nakamura H, Ohyama M, Osaka H, Kambara T, Hirako Y, Shimizu H. Natsuga K, et al. Hum Mutat. 2010 Oct;31(10):E1687-98. doi: 10.1002/humu.21330. Hum Mutat. 2010. PMID: 20665883 Free PMC article.
• Epidermolysis bullosa simplex associated with pyloric atresia is a novel clinical subtype caused by mutations in the plectin gene (PLEC1).
  Nakamura H, Sawamura D, Goto M, Nakamura H, McMillan JR, Park S, Kono S, Hasegawa S, Paku S, Nakamura T, Ogiso Y, Shimizu H. Nakamura H, et al. J Mol Diagn. 2005 Feb;7(1):28-35. doi: 10.1016/S1525-1578(10)60005-0. J Mol Diagn. 2005. PMID: 15681471 Free PMC article.
• Epidermolysis bullosa simplex with PLEC mutations: new phenotypes and new mutations.
  Charlesworth A, Chiaverini C, Chevrant-Breton J, DelRio M, Diociaiuti A, Dupuis RP, El Hachem M, Le Fiblec B, Sankari-Ho AM, Valhquist A, Wierzbicka E, Lacour JP, Meneguzzi G. Charlesworth A, et al. Br J Dermatol. 2013 Apr;168(4):808-14. doi: 10.1111/bjd.12202. Br J Dermatol. 2013. PMID: 23289980
• Novel PLEC Variant Causes Mild Skin Fragility, Pyloric Atresia, Muscular Dystrophy and Urological Manifestations.
  Valari M, Theodoraki M, Loukas I, Gkantseva-Patsoura S, Karavana G, Falaina V, Lykopoulou L, Pons R, Athanasiou I, Wertheim-Tysarowska K, Kanaka-Gantenbein C, Kiritsi D. Valari M, et al. Acta Derm Venereol. 2019 Dec 1;99(13):1309-1310. doi: 10.2340/00015555-3317. Acta Derm Venereol. 2019. PMID: 31513275 Review. No abstract available.
• Epidermolysis Bullosa with Pyloric Atresia.
  Lucky AW, Gorell E. Lucky AW, et al. 2008 Feb 22 [updated 2023 Jan 26]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. 2008 Feb 22 [updated 2023 Jan 26]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. PMID: 20301336 Free Books & Documents. Review.

References

REFERENCES

1. 1. Fine JD, Eady RA, Bauer EA, Bruckner-Tuderman L, Heagerty A, Hintner H, et al. The classification of inherited epidermolysis bullosa (EB): report of the third international consensus meeting on diagnosis and classification of EB. J Am Acad Dermatol. 2008;58:931-50.
2. 1. Pulkkinen L, Uitto J. Hemidesmosomal variants of epidermolysis bullosa. Mutations in the alpha6beta4 integrin and the 180-kD bullous pemphigoid antigen/type XVII collagen genes. Exp Dermatol. 1998;7:46-64.
3. 1. Charlesworth A, Gagnoux-Palacios L, Bonduelle M, Ortonne JP, De Raeve L, Meneguzzi G. Identification of a lethal form of epidermolysis bullosa simplex associated with a homozygous genetic mutation in plectin. J Invest Dermatol. 2003;121:1344-8.
4. 1. Ruzzi L, Gagnoux-Palacios L, Pinola M, Belli S, Meneguzzi G, D'Alessio M, et al. A homozygous mutation in the integrin alpha6 gene in junctional epidermolysis bullosa with pyloric atresia. J Clin Invest. 1997;99:2826-31.
5. 1. Vidal F, Aberdam D, Miquel C, Christiano AM, Pulkkinen L, Uitto J, et al. Integrin beta 4 mutations associated with junctional epidermolysis bullosa with pyloric atresia. Nat Genet. 1995;10:229-34.

MeSH terms

Substances

Supplementary concepts

LinkOut - more resources

• Full Text Sources

  • Ovid Technologies, Inc.
  • Wiley

• Miscellaneous

  • NCI CPTAC Assay Portal