Cantú syndrome is a
rare disorder characterised by congenital hypertrichosis, neonatal macrosomia,
distinct osteochondrodysplasia and cardiomegaly. Using an exome-sequencing
approach applied to one proband-parent trio and three unrelated single cases,
van Bon et al (PMID: 22608503) 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. The proposed pathogenic mechanism is that of an activation of the
final protein product. Of note, previously, loss-of-function mutations in this
gene have been associated with idiopathic dilated cardiomyopathy type 10
(CMD10).
References: see text.
