Array-CGH Analysis Suggests Genetic Heterogeneity in Rhombencephalosynapsis

Abstract

Rhombencephalosynapsis is an uncommon, but increasingly recognized, cerebellar malformation defined as vermian agenesis with fusion of the hemispheres. The embryologic and genetic mechanisms involved are still unknown, and to date, no animal models are available. In the present study, we used Agilent oligonucleotide arrays in a large series of 57 affected patients to detect candidate genes. Four different unbalanced rearrangements were detected: a 16p11.2 deletion, a 14q12q21.2 deletion, an unbalanced translocation t(2p;10q), and a 16p13.11 microdeletion containing 2 candidate genes. These genes were further investigated by sequencing and in situ hybridization. This first microarray screening of a rhombencephalosynapsis series suggests that there may be heterogeneous genetic causes.

Keywords: Array-CGH; Copy Number Variation; NDE1; Rhombencephalosynapsis.

Fig. 1

Patient 4. a Bilateral alopecia. b Abnormal transverse folial running across the midline.

Fig. 2

Expression of chick NDE1 at stage HH14 in whole embryos. a Lateral view. Left: in situ expression with the sense probe; right: in situ expression with the antisense probe. b Dorsal view. d = Diencephalon; mes = mesencephalon; met = metencephalon; mhb = midbrain-hindbrain boundary; ot = otic vesicle; r1-r5 = rhombomeres; t = telencephalon; v = optic vesicle. Bracket indicates the cerebellar territory in the hindbrain (metencephalon part).