Microdeletion of 6q16.1 encompassing EPHA7 in a child with mild neurological abnormalities and dysmorphic features: case report

Abstract

Background: Of the fewer than 100 cases reported within the literature of constitutional deletions involving the long arm of chromosome 6, only five have been characterized using high-resolution microarray analysis. Reported 6q deletion patients show a high incidence of mental retardation, ear anomalies, hypotonia, and postnatal growth retardation.

Results: We report a 16-month-old male presenting with developmental delay and dysmorphic features who was found by array-based comparative genomic hybridization (aCGH) to have a ~2.16 Mb de novo deletion within chromosome band 6q16.1 that encompasses only two genes. Expression studies of the mouse homologue of one of the genes, the ephrin receptor 7 gene (EPHA7), have shown the gene functions during murine embryogenesis to form cortical domains, determine brain size and shape, and play a role in development of the central nervous system (CNS).

Discussion: Our results suggest that deletion of EPHA7 plays a role in the neurologic and dysmorphic features, including developmental delay, hypotonia, and ear malformations, observed in some 6q deletion patients.

Figure 1

Proband at age 15 months. Note triangular-shaped face, mild ptosis on the left side, and cupped, posteriorly rotated ears.

Figure 2

Brain MRI showing (A) possible brain atrophy and possible hemorrhage, (B) slight thinning of the corpus collosum posteriorly and (C) decrease in white matter volume seen posteriorly in the cerebral hemispheres bilaterally.

Figure 3

Analysis of deletion encompassing EPHA7 on 6q16.1. (A) Oligonucleotide microarray plot showing a copy-number loss of 30 oligo probes spanning 2.16 Mb at 6q16.1 (chr6:92,836,995–94,905,920). Probes are ordered on the x-axis according to physical mapping positions with distal 6p to the left and distal 6q to the right. (B) FISH demonstrating deletion of EPHA7. BAC clone RP11-270O11 which encompasses EPHA7 was labeled in red and the centromere probe to chromosome 6 (D6Z1) was labeled in green as a control. One red signal was present, indicating deletion of EPHA7.

Figure 4

Zoomed view of 6q15-6q21. Blue bars represent minimal deletion sizes; black lines represent maximum deletion sizes for each patient based on gaps in microarray coverage. Bar A is the current case with a deletion size of 2.1 Mb. Bar B is Klein et al. [2] patient 2 with a deletion size of 6–16.2 Mb; Bar C is Klein et al. [2] patient 1 with deletion of size 8.8–16.4 Mb; Bar D is Klein et al. [2] patient 3 with deletion size of 11.3–15.7 Mb; Bar E is the patient presented by Le Caignec et al. [4] with deletion size of 12.9–15.7 Mb; Bar F is the patient presented by Zherebstov et al. [3] with deletion size of 34 Mb (the bar image for this deletion extends beyond the coordinates depicted). The dark blue band represents EPHA7.