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Autosomal recessive variants in the cytolinker gene PLEC have been reported in patients with congenital scalp skin absence characteristic of Aplasia Cutis Congenita. In a cohort study of over 600 patients with epidermolysis bullosa–related disorders, two unrelated individuals presented with ACC and carried biallelic PLEC variants, including a truncating allele c.9052G>T (p.Glu3018Ter) ([PMID:35815343]). No additional affected relatives have been described, and segregation data are limited.
While numerous functional studies of plectin deficiency demonstrate the protein’s essential role in skin integrity and hemidesmosome stability, none specifically address ACC pathogenesis. Plectin-null models exhibit skin blistering but have not been evaluated for focal scalp defects.
Together, the current evidence supports a Limited association between PLEC and autosomal recessive ACC, pending replication in additional families and ACC-specific functional assays. Key Take-home: PLEC sequencing should be considered in unexplained ACC, especially when other plectinopathy features are present.
Gene–Disease AssociationLimitedTwo unrelated probands with aplasia cutis congenita and biallelic PLEC variants; minimal segregation; no ACC-specific functional data ([PMID:35815343]) Genetic EvidenceLimited2 probands with biallelic PLEC variants presenting ACC ([PMID:35815343]) Functional EvidenceLimitedNo functional studies specific to ACC; plectin knockout models show skin fragility but lack ACC phenotype |