Two new cases with microdeletion of 17q23.2 suggest presence of a candidate gene for sensorineural hearing loss within this region

Abstract

Microdeletion of the 17q23.2 region has very recently been suggested as a new emerging syndrome based on the finding of 8 cases with common phenotypes including mild-to-moderate developmental delay, heart defects, microcephaly, postnatal growth retardation, and hand, foot, and limb abnormalities. In this report, we describe two new 17q23.2 deletion patients with mild intellectual disability and sensorineural hearing loss. They both had submicroscopic deletions smaller than the common deleted region for the 8 previously described 17q23.2 microdeletion cases. TBX4 was previously suggested as the responsible gene for the heart or limb defects observed in 17q23.2 deletion patients, but the present cases do not have these features despite deletion of this gene. The finding of sensorineural hearing loss in 5 of the 10 cases, including the present cases, with a microdeletion at17q23.2, strongly suggests the presence of a candidate gene for hearing loss within this region. We screened 41 patients with profound sensorineural hearing loss for mutations of TBX2 and detected no mutations.

Molecular and clinical delineation of the 17q22 microdeletion phenotype

“…However, there are some major differencies in the bone, joint and facial phenotypes, such as symphalangism and short palpebral fissures. 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.…”

Size matters: Large copy number losses in Hirschsprung disease patients reveal genes involved in enteric nervous system development

“…This phenotype overlaps with other patients with 17q22-q23 deletions [ 51 , 52 ]. One of the other patients is constipated, but HSCR disease has not been previously described [ 69 , 70 ]. Four “ENS genes” are included in the CNV of patient P_000567: BCAS3 , HEATR6 , TBX2 , USP32 , of which the latter two are a CCR.…”

Familial microduplication of 17q23.1–q23.2 involving TBX4 is associated with congenital clubfoot and reduced penetrance in females

“…Immediately flanked by highly homologous segmental duplications, 17q23 was identified as a chromosome region prone to unequal crossing‐over between paralogous segments that may result in clinically relevant copy‐number variations (CNVs) [Rudd et al, ]. Indeed, 17q23 deletions and duplications have been repeatedly associated with human congenital malformation syndromes involving craniofacial, cardiovascular, and skeletal structures [King et al, ; Alvarado et al, ; Ballif et al, ; Nimmakayalu et al, ; Radio et al, ; Lu et al, ; Schönewolf‐Greulich et al, ]. More specifically, duplication of the 17q23.1–q23.2 region has been reported to result in congenital clubfoot with variable penetrance and expressivity [Alvarado et al, ; Lu et al, ].…”

“…The family presented herein demonstrates high phenotypic variability and incomplete penetrance. Interestingly, 17q23.1–q23.2 deletion phenotypes are highly variable and include microcephaly, hearing loss, pulmonary hypertension, developmental delay, postnatal onset growth delay, heart defects, and limb abnormalities [Ballif et al, ; Nimmakayalu et al, ; Schönewolf‐Greulich et al, ]. Remarkably, Alvarado et al [] described a familial case of clubfoot in siblings with a 17q23.1–q23.2 deletion.…”