X-Linked Deafness-2 (DFNX2) Phenotype Associated With a Paracentric Inversion Upstream of
POU3F4Journal Articles
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Overview
abstract
Purpose
The authors report on a 7-year-old male, designated
FR,
who has severe sensorineural hearing loss. Features include a round face, hypertelorism, epicanthal folds, and flat nasal root. Although there were early developmental concerns regarding FR, all but his speech delay resolved when he was placed in an educational program that accommodated his hearing loss. Genetic studies were performed to investigate genetic causes for his hearing loss.
Method
History, physical examination, audiologic assessment, and imaging were performed according to usual practice.
FMR1,GJB2,GJB6,
and
POU3F4
genes were sequenced. Chromosomal studies consisted of karyotyping and breakpoint analysis by fluorescence in situ hybridization (FISH).
Results
Results from
FMR1,GJB2,GJB6,
and
POU3F4
sequencing and echocardiography, electrocardiogram, and abdominal ultrasound were normal. A computed tomography (CT) scan revealed a large fundus of the internal auditory canals and absence of the bony partition between the fundus and the adjacent cochlear turns, with a widened modiolus bilaterally. FR's CT findings were consistent with those described in persons with X-linked deafness-2 (DFNX2) hereditary deafness. FR's karyotype was 46,inv(X)(q13q24),Y.ish inv(X)(XIST+)mat. FISH refined the breakpoints to inv(X)(q21.1q22.3). The Xq21.1 breakpoint was narrowed to a 25-kb region 450 kb centromeric to the DFNX2 gene,
POU3F4
. There are rare case reports of DFNX2 patients with chromosomal rearrangements positioned centromeric to
POU3F4
and no mutations within the gene.
Conclusion
Authors hypothesized that FR's hearing loss was caused by dysregulation of
POU3F4
due to separation from regulatory elements affected by the inversion.
