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TGM1 encodes transglutaminase-1, a key enzyme for cornified envelope assembly in keratinocytes. Acral self-healing collodion baby is defined by a transient, extremity-limited collodion membrane that resolves spontaneously. In a single family, a proband presented at birth with collodion membrane confined to the extremities that normalized by 3 weeks, and her older sister exhibited generalized collodion membrane evolving into lamellar ichthyosis (n=2 affected individuals) (PMID:19500103). Both siblings were compound heterozygous for TGM1 variants: c.1075G>A (p.Val359Met) and c.1187G>A (p.Arg396His), with the sister also carrying a splice-site deletion c.1922_1926+2del.
Functional assays of recombinant TGase-1 proteins demonstrated residual activity of 12.8% for p.Val359Met and 3.3% for p.Arg396His, aligning with a partially preserved enzyme function that likely underlies the self-healing phenotype (PMID:19500103). Molecular diagnosis of TGM1 variants is critical for prognostic counseling and expands the clinical spectrum of TGase-1 deficiency.
Gene–Disease AssociationLimitedTwo affected siblings in one family with segregation and functional concordance Genetic EvidenceLimitedCompound heterozygous TGM1 variants identified in two probands from a single pedigree Functional EvidenceModerateRecombinant enzyme assays demonstrate significantly reduced TGase-1 activity for both variants |