A new case of de novo 19p13.2p13.12 deletion in a girl with overgrowth and severe developmental delay

Abstract

Background: We report clinical and molecular cytogenetic characterization of a 2 year-old girl with 19p13.2p13.12 microdeletion and compare her clinical features with those of three other patients reported before.

Result: Array comparative genomic hybridization (aCGH) revealed in the present patient a de novo microdeletion of 1.45 Mb within 19p13.2p13.12. The deletion includes seven OMIM genes: MAN2B1, RNASEH2A, KLF1, GCDH, NFIX, CACNA1A and CC2D1A.

Discussion: The present case and three other patients with partially overlapping 19p13 microdeletion share the following features: psychomotor and language delay, intellectual disability, seizures, hypotonia, skeletal anomalies and facial dysmorphism. The smallest region of overlapping between all four reported patients is around 300 kb and spans only two genes: NFIX and CACNA1A. Their haploinsufficincy could be the base for the phenotype -genotype correlation.

Keywords: 19p13.2p13.12 deletion; Array comparative genomic hybridization; Overgrowth; Psychomotor delay.

Figure 1

Photographs of the patient at age of 2 years and 3 months, frontal (a) and lateral (b) view. Note the tall forehead, anteverted nares, thin upper lip, anteverted ears and long philtrum.

Figure 2

aCGH result shows the extend of the 19p13.2p13.12 deletion in the patient, with breakpoints at genomic positions 12,691,241-14,141,544 (GRCHh37/hg19).

Figure 3

FISH analysis of the 19p13.2-p13.12 deletion. Spectrum-orange labeled BAC clone RP11-782D11 and spectrum-green labeled 19q subtelomeric (CTD-2265021) probe (Tel 19q) used for identification of chromosomes 19. Arrow indicate the absence of orange signal on chromosome del(19)(p13.2 ~ 13.12p13.2 ~ 13.12).

Figure 4

Schematic representation of 19p13.2-p13.12 region deleted in our patient and three other reported in the literature sharing about 300 kb indicated by color rectangle.