Cantú syndrome is caused by mutations in ABCC9.
Am J Hum Genet
; 90(6): 1094-101, 2012 Jun 08.
Article
em En
| MEDLINE
| ID: mdl-22608503
ABSTRACT
Cantú syndrome is a rare disorder characterized by congenital hypertrichosis, neonatal macrosomia, a distinct osteochondrodysplasia, and cardiomegaly. Using an exome-sequencing approach applied to one proband-parent trio and three unrelated single cases, we identified heterozygous mutations in ABCC9 in all probands. With the inclusion of the remaining cohort of ten individuals with Cantú syndrome, a total of eleven mutations in ABCC9 were found. The de novo occurrence in all six simplex cases in our cohort substantiates the presence of a dominant disease mechanism. All mutations were missense, and several mutations affect Arg1154. This mutation hot spot lies within the second type 1 transmembrane region of this ATP-binding cassette transporter protein, which may suggest an activating mutation. ABCC9 encodes the sulfonylurea receptor (SUR) that forms ATP-sensitive potassium channels (K(ATP) channels) originally shown in cardiac, skeletal, and smooth muscle. Previously, loss-of-function mutations in this gene have been associated with idiopathic dilated cardiomyopathy type 10 (CMD10). These findings identify the genetic basis of Cantú syndrome and suggest that this is a new member of the potassium channelopathies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteocondrodisplasias
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Receptores de Droga
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Cardiomegalia
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Transportadores de Cassetes de Ligação de ATP
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Canais de Potássio Corretores do Fluxo de Internalização
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Doenças Genéticas Ligadas ao Cromossomo X
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Hipertricose
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Mutação
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Child
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Am J Hum Genet
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Holanda