This site needs JavaScript to work properly. Please enable it to take advantage of the complete set of features!
Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Advanced
User Guide

Save citation to file

Add to Collections

Name must be less than 100 characters
Unable to load your collection due to an error
Please try again

Add to My Bibliography

Unable to load your delegates due to an error
Please try again

Your saved search

Test search terms
Would you like email updates of new search results?
Saved Search Alert Radio Buttons
()

Create a file for external citation management software

Your RSS Feed

. 2007 Feb;80(2):338-44.
doi: 10.1086/510920. Epub 2006 Dec 27.

Homozygous mutations in fibroblast growth factor 3 are associated with a new form of syndromic deafness characterized by inner ear agenesis, microtia, and microdontia

Mustafa Tekin  1 , Burcu Oztürk Hişmi, Suat Fitoz, Hilal Ozdağ, Filiz Başak Cengiz, Asli Sirmaci, Idil Aslan, Bora Inceoğlu, E Berrin Yüksel-Konuk, Seda Taşir Yilmaz, Oztan Yasun, Nejat Akar
Affiliations

Affiliation

  • 1 Division of Clinical Molecular Pathology and Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey. mtekin@medicine.ankara.edu.tr

Homozygous mutations in fibroblast growth factor 3 are associated with a new form of syndromic deafness characterized by inner ear agenesis, microtia, and microdontia

Mustafa Tekin et al. Am J Hum Genet. 2007 Feb.
. 2007 Feb;80(2):338-44.
doi: 10.1086/510920. Epub 2006 Dec 27.

Authors

Mustafa Tekin  1 , Burcu Oztürk Hişmi, Suat Fitoz, Hilal Ozdağ, Filiz Başak Cengiz, Asli Sirmaci, Idil Aslan, Bora Inceoğlu, E Berrin Yüksel-Konuk, Seda Taşir Yilmaz, Oztan Yasun, Nejat Akar

Affiliation

  • 1 Division of Clinical Molecular Pathology and Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey. mtekin@medicine.ankara.edu.tr

Abstract

We identified nine individuals from three unrelated Turkish families with a unique autosomal recessive syndrome characterized by type I microtia, microdontia, and profound congenital deafness associated with a complete absence of inner ear structures (Michel aplasia). We later demonstrated three different homozygous mutations (p.S156P, p.R104X, and p.V206SfsX117) in the fibroblast growth factor 3 (FGF3) gene in affected members of these families, cosegregating with the autosomal recessive transmission as a completely penetrant phenotype. These findings demonstrate the involvement of FGF3 mutations in a human malformation syndrome for the first time and contribute to our understanding of the role this gene plays in embryonic development. Of particular interest is that the development of the inner ear is completely disturbed at a very early stage--or the otic vesicle is not induced at all--in all of the affected individuals who carried two mutant FGF3 alleles.

PubMed Disclaimer

Figures

Figure 1.

Figure 1.

Pedigrees of three unrelated Turkish…

Figure 1.

Pedigrees of three unrelated Turkish families with the syndrome described in this report.…

Figure 1.
Pedigrees of three unrelated Turkish families with the syndrome described in this report. Plus and minus signs indicate the presence and absence of the identified mutation, respectively. Mutations were c.466T→C, c.310C→T, and c.616delG, in families A, B, and C, respectively. Although consanguinity was denied between I:1 and I:2 in family C and between II:5 and II:6 in family B, parents originated from a small, isolated village in both families. Consanguinity between II:3 and II:4 in family A is more distant than third-degree cousins.
Figure 2.

Figure 2.

Clinical photographs of the affected…

Figure 2.

Clinical photographs of the affected nine subjects. Note the presence of type I…

Figure 2.
Clinical photographs of the affected nine subjects. Note the presence of type I microtia and microdontia in all patients. A long face was seen in most affected subjects, growing more pronounced as they got older. A, From left to right, V:1, V:2, IV:5, IV:8, and IV:10 in family A. B, IV:3, IV:2, and III:3 in family B. C, II:1 in family C. The hearing members of the families have normal-appearing teeth and no craniofacial dysmorphology.
Figure 3.

Figure 3.

A, Contiguous axial CT sections…

Figure 3.

A, Contiguous axial CT sections of normal temporal bone. Cochlea ( white arrow …
Figure 3.
A, Contiguous axial CT sections of normal temporal bone. Cochlea (white arrow), internal auditory canal (asterisk), vestibule (black arrow), and ossicles (double white arrows) are clearly visible. B, CT images crossing through approximately the same levels, compared with normal sections, reveal petrous bone aplasia, with absence of inner ear structures in II:1 in family C. Normal development of middle ear cavity and ossicles (double arrow) are clearly visible. CT images in all affected subjects showed similar findings (fig. 4).
Figure 4.

Figure 4.

Contiguous axial CT sections of…

Figure 4.

Contiguous axial CT sections of normal temporal bone are shown in row A.…

Figure 4.
Contiguous axial CT sections of normal temporal bone are shown in row A. Cochlea (white arrow), internal auditory canal (asterisk), vestibule (black arrow) and ossicles (double white arrow) are well seen. CT images approximately crossing through the same levels compared with normal sections reveal petrous bone aplasia or hypoplasia and absence of inner ear structures and internal auditory canal in affected subjects (B–J). Individuals V:1, V:2, IV:5, IV:8, IV:10 in family A; IV:3, IV:2, III:3 in family B; and II:1 in family C are presented in panels B–F; G–I; and J, respectively.
Figure 5.

Figure 5.

In a patient (family C,…

Figure 5.

In a patient (family C, II:1) with bilateral inner ear petrous bone aplasia…

Figure 5.
In a patient (family C, II:1) with bilateral inner ear petrous bone aplasia and absence of inner ear structures detected on CT (row B in fig. 3), coronal (A) and axial (B) MR images clearly show the absence of the internal auditory canal in cerebellopontine angle compared with normal appearances (C and D). White arrows, cochleovestibular nerves.
Figure 6.

Figure 6.

A, Graphical representation of the…

Figure 6.

A, Graphical representation of the genomewide parametric two-point linkage analysis performed using 10K…
Figure 6.
A, Graphical representation of the genomewide parametric two-point linkage analysis performed using 10K GeneChip array in 19 members of family A. The top 15 two-point LOD scores are listed. B, Graphical representation of the parametric multipoint linkage analysis of chromosome 11 in 19 members of family A. C, Haplotypes manually created from genotypes of SNPs flanking the FGF3 gene, which were obtained using the 10K GeneChip array in 19 members of family A. Haplotypes in individual III:2 are not shown, because meiotic phases are unknown. Genotypes of SNPs rs1404501, rs490192, rs1944130, and rs2077955 from table 1 are not included, because they are not informative. Markers rs953894 and rs1279293 correspond to 58.15 cM and 70.05 cM on chromosome 11 in the Affymetrix Marshfield SNP database.
Figure 7.

Figure 7.

The c.466T→C (p.S156P), c.310C→T (p.R104X),…

Figure 7.

The c.466T→C (p.S156P), c.310C→T (p.R104X), and c.616delG (p.V206SfsX117) mutations. Arrows and lines indicate…

Figure 7.
The c.466T→C (p.S156P), c.310C→T (p.R104X), and c.616delG (p.V206SfsX117) mutations. Arrows and lines indicate the mutation points.
Figure 8.

Figure 8.

Serine at position 156 of …

Figure 8.

Serine at position 156 of Fgf3 is conserved in a variety of organisms…

Figure 8.
Serine at position 156 of Fgf3 is conserved in a variety of organisms from fish to frogs to humans. Data were obtained using protein-protein BLAST at the National Center for Biotechnology Information Web site.
See this image and copyright information in PMC

References

Web Resources

    1. Ensembl database, http://www.ensembl.org/Homo_sapiens/index.html (for FGF3 [accession number ENSG00000186895])
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for LADD syndrome)
    1. Primer3, http://frodo.wi.mit.edu/cgi-bin/primer3/primer3_www.cgi
    1. Protein-protein BLAST, http://www.ncbi.nlm.nih.gov/blast/Blast.cgi

References

    1. Morton CC, Nance WE (2006) Newborn hearing screening—a silent revolution. N Engl J Med 354:2151–2164 10.1056/NEJMra050700 - DOI - PubMed
    1. Bamiou DE, Phelps P, Sirimanna T (2000) Temporal bone computed tomography findings in bilateral sensorineural hearing loss. Arch Dis Child 82:257–260 10.1136/adc.82.3.257 - DOI - PMC - PubMed
    1. Mafong DD, Shin EJ, Lalwani AK (2002) Use of laboratory evaluation and radiologic imaging in the diagnostic evaluation of children with sensorineural hearing loss. Laryngoscope 112:1–7 10.1097/00005537-200201000-00001 - DOI - PubMed
    1. Michel P (1863) Memoire sur les anomalies congenitales de poreille intern. Gazette Med de Strasburg 23:55–58
    1. Allanson J (2004) Genetic hearing loss associated with external ear abnormalities. In: Toriello HV, Reardon W, Gorlin RJ (eds) Hereditary hearing loss and its syndromes. Oxford University Press, Oxford, pp 101–102

Publication types

Substances

Full text links
Elsevier Science full text link Elsevier Science Free PMC article
Cite
Morty Proxy This is a proxified and sanitized view of the page, visit original site.