Characterization of TGM1 c.984+1G>A mutation identified in a homozygous carrier of lamellar ichthyosis.
Int J Dermatol
; 51(4): 427-30, 2012 Apr.
Article
en En
| MEDLINE
| ID: mdl-22435431
BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) is a rare, nonsyndromic, heterogeneous disorder of cornification. It is divided into three clinical subtypes: lamellar ichthyosis (LI); congenital ichthyosiform erythroderma; and harlequin ichthyosis. In the majority of patients, LI is caused by transglutaminase-1 (TGase1) deficiency resulting from mutations in both copies of the transglutaminase 1 (TGM1) gene in chromosome 14. CASE REPORT: We report a patient with a severe LI phenotype who has a homozygous putative splicing mutation in the TGM1 gene. Our aim is to assess the pathologic effect of the TGM1 c.984+1G>A by splicing assays and bioinformatic tools. RESULTS: c.984+1G>A mutation created two alternative TGM1 mRNA splice variants that included 30 or 32 nucleotides of the 5' of intron 6. At the protein level, the partial in-frame aberrant transcript retaining 30 bp of intron 6 led to the insertion of 10 amino acids (p.Met329_Val330ins10) at the catalytic core domain of TGM1 protein (codons 247-572), whereas the transcript with the insertion of 32 nucleotides is predicted to encode a truncated protein (p.Val330MetfsX12). CONCLUSION: Our splicing assay, together with bioinformatic prediction tools, supports the pathological effect of the recently identified c.984+1G>A mutation in the TGM1 gene and unravels the molecular mechanism by which c.984+1G>A acts.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transglutaminasas
/
Ictiosis Lamelar
/
Mutación
Tipo de estudio:
Prognostic_studies
Límite:
Child
/
Female
/
Humans
Idioma:
En
Revista:
Int J Dermatol
Año:
2012
Tipo del documento:
Article
País de afiliación:
España
Pais de publicación:
Reino Unido