PMC8504801_01
The developmental anomalies of the proband. (A) Patient shows facial dysmorphism. (B) Computerized tomography scan shows tympanosclerosis and blockage of the ear canals. (C) Echocardiogram showing a 1.1 cm atrial septal defect.
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F1
A 3-month-old female infant, presenting with mild developmental delay and facial dysmorphism (Figure 1A), was admitted due to a failed newborn hearing screen. ABR test, evoked potentials were observed for the left ear, but not the right ear, at 80 and 90 dB stimuli. A computed tomography (CT) scan showed that both ears, but primarily the right ear, presented with tympanosclerosis, in addition to a blockage of the right ear canal (Figure 1B). In addition to the hearing deficit, an echocardiogram revealed a 1.1 cm atrial septal defect (ASD) and hypertrophy of right atrium and right ventricle, indicating congenital heart disease (Figure 1C).
The 1q21 microduplications or microdeletions of the proband, her mother and other reported patients with hearing problem. (A) Copy number analysis of the proband and her parents by next generation sequencing. (B) Positional plots of the microduplications and microdeletions on 1q21.1 and 1q21.2 regions (http://genome.ucsc.edu). (C) Confirmation of the proband's microduplication by CytoScan HD array.
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F2
A microduplication (copy number = 3) on chromosome 1 was observed in the proband and maternal genomic DNA, but was lacking from the paternal genome (Figure 2A). The microduplication in the proband (chr1:148,511,359-148,954,460) was distinct from that of her mother (chr1:148,771,265-149,026,439), although both duplications arose on chromosome 1q21.2 and the duplicated fragments largely overlapped (Figure 2B). Chromosome microarray of the proband's genomic DNA confirmed the 1q21.2 microduplication (Figure 2C). Consistent with this observation, and expanding upon it, NBPF genes are repeatedly found to be involved in the 1q21 microduplication or microdeletion in patients with congenital hearing deficits (Figure 2B).