Terminal osseous dysplasia is caused by a single recurrent mutation in the FLNA gene.
Am J Hum Genet
; 87(1): 146-53, 2010 Jul 09.
Article
en En
| MEDLINE
| ID: mdl-20598277
Terminal osseous dysplasia (TOD) is an X-linked dominant male-lethal disease characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin, and recurrent digital fibroma with onset in female infancy. After performing X-exome capture and sequencing, we identified a mutation at the last nucleotide of exon 31 of the FLNA gene as the most likely cause of the disease. The variant c.5217G>A was found in six unrelated cases (three families and three sporadic cases) and was not found in 400 control X chromosomes, pilot data from the 1000 Genomes Project, or the FLNA gene variant database. In the families, the variant segregated with the disease, and it was transmitted four times from a mildly affected mother to a more seriously affected daughter. We show that, because of nonrandom X chromosome inactivation, the mutant allele was not expressed in patient fibroblasts. RNA expression of the mutant allele was detected only in cultured fibroma cells obtained from 15-year-old surgically removed material. The variant activates a cryptic splice site, removing the last 48 nucleotides from exon 31. At the protein level, this results in a loss of 16 amino acids (p.Val1724_Thr1739del), predicted to remove a sequence at the surface of filamin repeat 15. Our data show that TOD is caused by this single recurrent mutation in the FLNA gene.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trastornos de la Pigmentación
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Enfermedades del Desarrollo Óseo
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Neoplasias Óseas
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Proteínas Contráctiles
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Enfermedades Genéticas Ligadas al Cromosoma X
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Fibroma
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Proteínas de Microfilamentos
Límite:
Adult
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Child, preschool
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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:
2010
Tipo del documento:
Article
País de afiliación:
Países Bajos
Pais de publicación:
Estados Unidos