Facial dysgenesis: A novel facial syndrome with chromosome 7 deletion p15.1-21.1

Julie E Hoover Fong, J. Cai, C. B. Cargile, G. H. Thomas, A. Patel, C. A. Griffin, E. W. Jabs, Ada Hamosh

Research output: Contribution to journalArticle

Abstract

We describe a female neonate with a unique constellation of features including anophthalmia and cryptophthalmos, temporal remnant "eye tags," bilateral cleft lip, unilateral cleft palate, a proboscis with absent nasal septum, choanal atresia, micrognathia, square stoma, and bilateral external auditory canal atresia. Gross brain structure, pituitary function, limbs, trunk, and genitalia were normal. Skeletal survey, echocardiogram and abdominal viscera were unremarkable except for a split central sinus of the right kidney. BAER exam indicated she could hear and temporal CT confirmed the presence of cochlea and possible ossicles. Cytogenetic evaluation revealed an interstitial deletion at chromosome 7p15.1-21.1. TWIST, a gene encoding a transcription factor involved in craniofacial development, is deleted by FISH analysis. The absence of a mutation on the non-deleted allele of TWIST as determined by sequencing virtually eliminates complete loss of the TWIST gene as the cause of this patient's severe phenotype. The HOXA gene cluster also encodes transcription factors that are crucial for directing cephalad to caudad somatic fetal development. HOXA1, the most telomeric of the 13 members of the HOXA gene cluster, is located at the centromeric boundary of the patient's chromosome 7 deletion. By FISH analysis, neither allele of HOXA1 is deleted and sequencing reveals no mutations. Haploin-sufficiency or complete loss of the HOXA1 gene also does not appear to cause this patient's severe phenotype. Previous reports of chromosome 7p15-21 deletions do not have phenotypes similar to this patient.

Original languageEnglish (US)
Pages (from-to)47-56
Number of pages10
JournalAmerican Journal of Medical Genetics
Volume117 A
Issue number1
StatePublished - Feb 15 2003

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Chromosome Deletion
Chromosomes, Human, Pair 7
Multigene Family
Phenotype
Micrognathism
Transcription Factors
Alleles
Anophthalmos
Choanal Atresia
Genes
Nasal Septum
Chromosomes, Human, Pair 21
Mutation
Ear Canal
Genitalia
Viscera
Cleft Lip
Cochlea
Cleft Palate
Fetal Development

Keywords

  • Anophthalmia
  • Chromosome 7
  • Cleft lip/palate
  • Cryptophthalmos
  • HOXA1
  • TWIST

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Facial dysgenesis : A novel facial syndrome with chromosome 7 deletion p15.1-21.1. / Hoover Fong, Julie E; Cai, J.; Cargile, C. B.; Thomas, G. H.; Patel, A.; Griffin, C. A.; Jabs, E. W.; Hamosh, Ada.

In: American Journal of Medical Genetics, Vol. 117 A, No. 1, 15.02.2003, p. 47-56.

Research output: Contribution to journalArticle

Hoover Fong, JE, Cai, J, Cargile, CB, Thomas, GH, Patel, A, Griffin, CA, Jabs, EW & Hamosh, A 2003, 'Facial dysgenesis: A novel facial syndrome with chromosome 7 deletion p15.1-21.1', American Journal of Medical Genetics, vol. 117 A, no. 1, pp. 47-56.
Hoover Fong JE, Cai J, Cargile CB, Thomas GH, Patel A, Griffin CA et al. Facial dysgenesis: A novel facial syndrome with chromosome 7 deletion p15.1-21.1. American Journal of Medical Genetics. 2003 Feb 15;117 A(1):47-56.
Hoover Fong, Julie E ; Cai, J. ; Cargile, C. B. ; Thomas, G. H. ; Patel, A. ; Griffin, C. A. ; Jabs, E. W. ; Hamosh, Ada. / Facial dysgenesis : A novel facial syndrome with chromosome 7 deletion p15.1-21.1. In: American Journal of Medical Genetics. 2003 ; Vol. 117 A, No. 1. pp. 47-56.
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