PMID- 24096866
OWN - NLM
STAT- MEDLINE
DCOM- 20150630
LR  - 20211203
IS  - 1558-9137 (Electronic)
IS  - 1059-0889 (Print)
IS  - 1059-0889 (Linking)
VI  - 23
IP  - 1
DP  - 2014 Mar
TI  - X-linked deafness-2 (DFNX2) phenotype associated with a paracentric inversion 
      upstream of POU3F4.
PG  - 1-6
LID - 10.1044/1059-0889(2013/13-0018) [doi]
AB  - 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.
FAU - Anger, Gregory J
AU  - Anger GJ
FAU - Crocker, Susan
AU  - Crocker S
FAU - McKenzie, Kyle
AU  - McKenzie K
FAU - Brown, Kerry K
AU  - Brown KK
FAU - Morton, Cynthia C
AU  - Morton CC
FAU - Harrison, Karen
AU  - Harrison K
FAU - MacKenzie, Jennifer J
AU  - MacKenzie JJ
LA  - eng
GR  - P01 GM061354/GM/NIGMS NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Am J Audiol
JT  - American journal of audiology
JID - 9114917
RN  - 0 (Connexins)
RN  - 0 (GJB2 protein, human)
RN  - 0 (POU Domain Factors)
RN  - 0 (POU3F4 protein, human)
RN  - 127120-53-0 (Connexin 26)
RN  - Progressive hearing loss stapes fixation
SB  - IM
MH  - Child
MH  - *Chromosome Inversion
MH  - Chromosomes, Human, X/*genetics
MH  - Connexin 26
MH  - Connexins
MH  - Genetic Diseases, X-Linked/*genetics/physiopathology
MH  - Genotype
MH  - Hearing Loss, Conductive/*genetics/physiopathology
MH  - Hearing Loss, Sensorineural/*genetics/physiopathology
MH  - Humans
MH  - Male
MH  - POU Domain Factors/*genetics
MH  - Phenotype
PMC - PMC4644427
MID - NIHMS706255
EDAT- 2013/10/08 06:00
MHDA- 2015/07/01 06:00
PMCR- 2015/11/14
CRDT- 2013/10/08 06:00
PHST- 2013/10/08 06:00 [entrez]
PHST- 2013/10/08 06:00 [pubmed]
PHST- 2015/07/01 06:00 [medline]
PHST- 2015/11/14 00:00 [pmc-release]
AID - 1059-0889_2013_13-0018 [pii]
AID - 10.1044/1059-0889(2013/13-0018) [doi]
PST - ppublish
SO  - Am J Audiol. 2014 Mar;23(1):1-6. doi: 10.1044/1059-0889(2013/13-0018).