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
Case Reports
. 2007 May 15;143A(10):1053-9.
doi: 10.1002/ajmg.a.31715.

Mandibulofacial dysostosis in a patient with a de novo 2;17 translocation that disrupts the HOXD gene cluster

David A Stevenson  1 , Steven B Bleyl, Teresa Maxwell, Arthur R Brothman, Sarah T South
Affiliations
Case Reports

Mandibulofacial dysostosis in a patient with a de novo 2;17 translocation that disrupts the HOXD gene cluster

David A Stevenson et al. Am J Med Genet A. .

Abstract

Treacher Collins syndrome (TCS) is the prototypical mandibulofacial dysostosis syndrome, but other mandibulofacial dysostosis syndromes have been described. We report an infant with mandibulofacial dysostosis and an apparently balanced de novo 2;17 translocation. She presented with severe lower eyelid colobomas requiring skin grafting, malar and mandibular hypoplasia, bilateral microtia with external auditory canal atreasia, dysplastic ossicles, hearing loss, bilateral choanal stenosis, cleft palate without cleft lip, several oral frenula of the upper lip/gum, and micrognathia requiring tracheostomy. Her limbs were normal. Chromosome analysis at the 600-band level showed a 46,XX,t(2;17)(q24.3;q23) karyotype. Sequencing of the entire TCOF1 coding region did not show evidence of a sequence variation. High-resolution genomic microarray analysis did not identify a cryptic imbalance. FISH mapping refined the breakpoints to 2q31.1 and 17q24.3-25.1 and showed the 2q31.1 breakpoint likely affects the HOXD gene cluster. Several atypical findings and lack of an identifiable TCOF1 mutation suggest that this child has a provisionally unique mandibulofacial dysostosis syndrome. The apparently balanced de novo translocation provides candidate loci for atypical and TCOF1 mutation negative cases of TCS. Based on the agreement of our findings with one previous case of mandibulofacial dysostosis with a 2q31.1 transocation, we hypothesize that misexpression of genes in the HOXD gene cluster produced the described phenotype in this patient.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Photographs of patient: (A) in infancy; (B) after lower eyelid reconstruction; (C) after oral frenulae release also showing cleft palate (arrow points to one remnant of oral frenulae). (D) Partial karyogram of normal and derivative chromosomes 2 and 17.
Figure 2
Figure 2
High resolution CGH of the breakpoint intervals. Ratio plots for the 2q31.1 (top) and 17q24.3–25.1 (bottom) regions. No gains (relative ratio > 0.45) or losses (relative ratio < 0.85) of genetic material were detected across these intervals.
Figure 3
Figure 3
(A) Metaphase FISH using BAC probe RP11-387A1 shows that this clone spans the 2q31.1 breakpoint with signals on the normal chromosome 2 and on both the der2 and der17 chromosomes. (B) Map of the 2q31.1 breakpoint (chr2:176,450,000–176,900,000) shows that the disrupted BAC (RP11-387A1) spans a 176 Kb region that includes most of the HOXD gene cluster and EVX2 gene (shown boxed) as well as approximately 50 Kb of upstream sequence. Two other genes in the region (shown as labeled arrows) lie outside the disrupted BAC. (C) Map of the 17q24.3–25.1 breakpoint (chr17:68,165,340–70,882,076). FISH mapping of a proximal BAC (RP11-65C22) and distal BAC (RP11-76G4) maps the breakpoint to a 2.5 Mb interval that contains approximately 34 genes (shown as unlabeled arrows).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Akarsu AN, Stoilov I, Yilmaz E, Sayli BS, Sarfarazi M. Genomic structure of HOXD13 gene: a nine polyalanine duplication causes synpolydactyly in two unrelated families. Hum Mol Genet. 1996;5(7):945–952. - PubMed
    1. Arn PH, Mankinen C, Jabs EW. Mild mandibulofacial dysostosis in a child with a deletion of 3p. Am J Med Genet. 1993;46:534–536. - PubMed
    1. Balestrazzi P, Baeteman MA, Mattei MG, Mattei JF. Franceschetti syndrome in a child with a de novo balanced translocation (5;13)(q11;p11) and significant decrease of hexosaminidase, B. Hum Genet. 1983;64:305–308. - PubMed
    1. Condie BG, Capecchi M. Mice homozygous for a targeted disruption of Hoxd-3 (Hox4-1) exhibit anterior transformations of the first and second cervical vertebrae, the atlas and the axis. Development. 1993;119:579–595. - PubMed
    1. Delb W, Lipfert S, Henn W. Mandibulofacial dysostosis, microcephaly and thorax deformities in two brothers: a new recessive syndrome? Clin Dysmorphol. 2001;10:105–109. - PubMed

Publication types

Substances