Novel domain-specific POU3F4 mutations are associated with X-linked deafness: examples from different populations.
BACKGROUND
Mutations in the POU3F4 gene cause X-linked deafness type 3 (DFN3), which is characterized by inner ear anomalies.


METHODS
Three Turkish, one Ecuadorian, and one Nigerian families were included based on either inner ear anomalies detected in probands or X-linked family histories. Exome sequencing and/or Sanger sequencing were performed in order to identify the causative DNA variants in these families.


RESULTS
Four novel, c.707A>C (p.(Glu236Ala)), c.772delG (p.(Glu258ArgfsX30)), c.902C>T (p.(Pro301Leu)), c.987T>C (p.(Ile308Thr)), and one previously reported mutation c.346delG (p.(Ala116ProfsX26)) in POU3F4, were identified. All mutations identified are predicted to affect the POU-specific or POU homeo domains of the protein and co-segregated with deafness in all families.


CONCLUSIONS
Expanding the spectrum of POU3F4 mutations in different populations along with their associated phenotypes provides better understanding of their clinical importance and will be helpful in clinical evaluation and counseling of the affected individuals.
John P. Hussmann Institute for Human Genomics and John T. Macdonald Foundation, Department of Human Genetics, Miller school of Medicine, University of Miami, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA. g.bademci@med.miami.edu.
Guney
G
Bademci
John P. Hussmann Institute for Human Genomics and John T. Macdonald Foundation, Department of Human Genetics, Miller school of Medicine, University of Miami, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA. akeemlasisi@gmail.com.|Department of Otorhinolaryngology, College of Medicine, University of Ibadan, Ibadan, Nigeria. akeemlasisi@gmail.com.
Akeem
A
Lasisi
John P. Hussmann Institute for Human Genomics and John T. Macdonald Foundation, Department of Human Genetics, Miller school of Medicine, University of Miami, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA. koyariz@gmail.com.
Kemal O
KO
Yariz
Departamento de Genetica, Hospital de Especialidades FFAA, Quito, Ecuador. paom14@gmail.com.
Paola
P
Montenegro
John P. Hussmann Institute for Human Genomics and John T. Macdonald Foundation, Department of Human Genetics, Miller school of Medicine, University of Miami, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA. IMenendez1@med.miami.edu.
Ibis
I
Menendez
Departamento de Genetica, Hospital de Especialidades FFAA, Quito, Ecuador. genmolhg1@gmail.com.
Rodrigo
R
Vinueza
Departamento de Genetica, Hospital de Especialidades FFAA, Quito, Ecuador. charoparedes@yahoo.fr.
Rosario
R
Paredes
Departamento de Genetica, Hospital de Especialidades FFAA, Quito, Ecuador. germaniamoreta@yahoo.com.
Germania
G
Moreta
John P. Hussmann Institute for Human Genomics and John T. Macdonald Foundation, Department of Human Genetics, Miller school of Medicine, University of Miami, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA. asuzak78@hotmail.com.|Department of Medical Genetics, Izmir Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey. asuzak78@hotmail.com.
Asli
A
Subasioglu
John P. Hussmann Institute for Human Genomics and John T. Macdonald Foundation, Department of Human Genetics, Miller school of Medicine, University of Miami, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA. SBlanton@med.miami.edu.
Susan
S
Blanton
Department of Radiodiagnostics, Ankara University School of Medicine, Ankara, Turkey. sfitoz@yahoo.com.
Suat
S
Fitoz
Department of Otorhinolaryngology, Eskisehir Osmangazi University School of Medicine, Eskisehir, Turkey. armaganincesulu@yahoo.com.
Armagan
A
Incesulu
Department of Otorhinolaryngology, Hacettepe University School of Medicine, Ankara, Turkey. lsennaroglu@gmail.com.
Levent
L
Sennaroglu
John P. Hussmann Institute for Human Genomics and John T. Macdonald Foundation, Department of Human Genetics, Miller school of Medicine, University of Miami, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA. mtekin@med.miami.edu.
Mustafa
M
Tekin
D002675:Child, Preschool; D015331:Cohort Studies; D003638:Deafness / Q000208:ethnology / Q000235:genetics*; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D050809:POU Domain Factors / Q000737:chemistry* / Q000235:genetics*; D010375:Pedigree; D017434:Protein Structure, Tertiary
D050809:POU Domain Factors; C091774:POU3F4 protein, human