A de novo 3.54 Mb deletion of 17q22‐q23.1 associated with hydrocephalus: A case report and review of literature

Abstract

We describe a female newborn with a de novo 3.54 megabase (Mb) deletion of 17q22-q23.1 (chr17:53,072,536-56,612,662, hg18) including genes from MSI2 to BCAS3 detected by oligonucleotide array comparative genomic hybridization (aCGH). Prenatal ultrasound examination noted oligohydramnios and ventriculomegaly in the fetus. Postnatal examination found hypotonia, macrocephaly, arachnodactyly of fingers and toes, dysmorphic features, bilateral hearing loss and heart defect. Review of reported cases with genomic findings noted one case with proximal deletion involving the NOG gene and a case series with distal recurrent microdeletions involving the TBX2 and TBX4 genes. Our case presented a unique deletion partially overlapped with the above deletions but not including the NOG, TBX2, and TBX4 genes. A genomic map for deletions in this 17q22-q23.1 region was constructed to further define the common deletion intervals for potential haplo-insufficient genes.

Molecular and clinical delineation of the 17q22 microdeletion phenotype

“…All patients with 17q23.1q23.2 deletions presented with heart defects, which is not the case with the 17q22 microdeletion patients, except for the above mentioned patient 1 with aortic hypoplasia and the patient reported by Khattab et al 6,30,31 Figure 3 Schematic representation of the size and location of 17q22 microdeletions detected by array-CGH in patients described here (black bars) and previously described patients with similar microdeletions (gray bars). 4,[6][7][8] Displayed and magnified chromosomal region is boxed in red on chromosome 17 at the top. The numbers below represent the genomic distance (in base pairs) from the 17p telomere according to UCSC Genome Browser Build 37/hg19 (2009).…”

“…Symphalangism, dysmorphic facial features and intellectual disability have previously been reported in four 17q22 microdeletion patients 4,[6][7][8] (Table 2). In addition, eight patients with similar phenotype and cytogenetically visible deletions between 17q22 and 17q24 have been reported.…”

“…Patient 6 also had a deletion involving these genes but no cardiac abnormality. It is notable that the patient with a 3.54-Mb microdeletion of 17q22-17q23.1, reported by Khattab et al 6 had heart anomalies, pulmonary hypertension and deletion of MKS1 but not NOG. This patient also had symphalangism, which might indicate positional effects of other genes in the region in the development of symphalangism.…”

“…Eight patients with deletions encompassing 17q22 have been reported previously. [1][2][3][4][5][6][7][8] Four of these were identified using array comparative genomic hybridization (array-CGH) or flourescent in situ hybridization (FISH), 4,[6][7][8] and of these, two involved the NOG gene. 4,8 There have been also three reported patients with NOG-like features, where NOG was considered not to be involved; however, these were assessed using standard karyotyping with poor resolution of breakpoints.…”

Fluorescence In situ Hybridization: Cell-Based Genetic Diagnostic and Research Applications

“…For many newly defined loci of genomic disorders and interstitial imbalances, there are no commercially available FISH probes. Therefore, “home-brew” targeted BAC clone FISH probes were used for these unique cases (Li et al, 2006; Khattab et al, 2011). …”