Cantu Syndrome Is Caused by Mutations in ABCC9


van Bon B. W. M. , Gilissen C., Grange D. K. , Hennekam R. C. M. , Kayserili H., Engels H., ...Daha Fazla

AMERICAN JOURNAL OF HUMAN GENETICS, cilt.90, ss.1094-1101, 2012 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 90 Konu: 6
  • Basım Tarihi: 2012
  • Doi Numarası: 10.1016/j.ajhg.2012.04.014
  • Dergi Adı: AMERICAN JOURNAL OF HUMAN GENETICS
  • Sayfa Sayıları: ss.1094-1101

Özet

Cantu 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 Cantu 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 Cantu syndrome and suggest that this is a new member of the potassium channelopathies.