Molecular and clinical delineation of the 17q22 microdeletion phenotype

Abstract

Deletions involving 17q21-q24 have been identified previously to result in two clinically recognizable contiguous gene deletion syndromes: 17q21.31 and 17q23.1-q23.2 microdeletion syndromes. Although deletions involving 17q22 have been reported in the literature, only four of the eight patients reported were identified by array-comparative genomic hybridization (array-CGH) or flourescent in situ hybridization. Here, we describe five new patients with 1.8-2.5-Mb microdeletions involving 17q22 identified by array-CGH. We also present one patient with a large karyotypically visible deletion involving 17q22, fine-mapped to B8.2 Mb using array-CGH. We show that the commonly deleted region in our patients spans 0.24 Mb and two genes; NOG and C17ORF67. The function of C17ORF67 is not known, whereas Noggin, the product of NOG, is essential for correct joint development. In common with the 17q22 patients reported previously, the disease phenotype of our patients includes intellectual disability, attention deficit hyperactivity disorder, conductive hearing loss, visual impairment, low set ears, facial dysmorphology and limb anomalies. All patients displayed NOG-related bone and joint features, including symphalangism and facial dysmorphology. We conclude that these common clinical features indicate a novel clinically recognizable, 17q22 contiguous microdeletion syndrome.

Delineation of the clinically recognizable 17q22 contiguous gene deletion syndrome in a patient carrying the smallest microdeletion known to date

“…Here, we describe a patient with the smallest known deletion affecting only the 17q22 region, which not only supports the findings of Laurell et al [], but also allows to further delineate the phenotype assigned to this region.…”

“…Here, we describe the first reported patient with the 17q22 contiguous microdeletion syndrome since its recent identification by Laurell et al []. To better delineate this new 17q22 contiguous gene microdeletion syndrome, we compared the clinical and molecular characteristics of the 10 patients studied by Laurell et al [], and the patient that we describe here.…”

“…Here, we describe the first reported patient with the 17q22 contiguous microdeletion syndrome since its recent identification by Laurell et al []. To better delineate this new 17q22 contiguous gene microdeletion syndrome, we compared the clinical and molecular characteristics of the 10 patients studied by Laurell et al [], and the patient that we describe here. Figure shows the nine deletions in the 10 patients (Patients 4 and 5 in Laurell et al [] share the same deletion) using the UCSC Genome Browser, hg38 assembly (http://genome.ucsc.edu/).…”

“…Recently, Laurell et al [] described a new clinically recognizable 17q22 contiguous microdeletion syndrome. This is one of three microdeletions in the chromosome 17q21–q24 region.…”

“…The other two microdeletions affect chromosome bands 17q21.31 (OMIM#610443); and 17q23.1–q23.2 (OMIM#613355). Laurell et al [] considered the need for descriptions of additional patients with microdeletions at 17q22, in order to elucidate the clinical and molecular characteristics of this new contiguous gene syndrome.…”