Cole Disease Results from Mutations in ENPP1.
Am J Hum Genet
; 93(4): 752-7, 2013 Oct 03.
Article
en En
| MEDLINE
| ID: mdl-24075184
ABSTRACT
The coexistence of abnormal keratinization and aberrant pigmentation in a number of cornification disorders has long suggested a mechanistic link between these two processes. Here, we deciphered the genetic basis of Cole disease, a rare autosomal-dominant genodermatosis featuring punctate keratoderma, patchy hypopigmentation, and uncommonly, cutaneous calcifications. Using a combination of exome and direct sequencing, we showed complete cosegregation of the disease phenotype with three heterozygous ENPP1 mutations in three unrelated families. All mutations were found to affect cysteine residues in the somatomedin-B-like 2 (SMB2) domain in the encoded protein, which has been implicated in insulin signaling. ENPP1 encodes ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which is responsible for the generation of inorganic pyrophosphate, a natural inhibitor of mineralization. Previously, biallelic mutations in ENPP1 were shown to underlie a number of recessive conditions characterized by ectopic calcification, thus providing evidence of profound phenotypic heterogeneity in ENPP1-associated genetic diseases.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pirofosfatasas
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Enfermedades de la Piel
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Calcificación Fisiológica
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Poroqueratosis
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Hipopigmentación
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Hidrolasas Diéster Fosfóricas
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Queratosis
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Mutación
Límite:
Female
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Humans
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Infant
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Male
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Newborn
Idioma:
En
Revista:
Am J Hum Genet
Año:
2013
Tipo del documento:
Article
País de afiliación:
Israel