Role of rare cases in deciphering the mechanisms of congenital anomalies: CHARGE syndrome research

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

In this review, our work on CHARGE syndrome will be used to exemplify the role of rare cases in birth defects research. The analysis of 29 cases with mutations of CHD7, the causative gene for CHARGE syndrome, clarified the relative importance of the cardinal features, including facial nerve palsy and facial asymmetry. Concurrently, in situ hybridization using chick embryos studies were performed to delineate the expression pattern of Chd7. The Chd7-positive regions in the chick embryos and the anatomical defects commonly seen in patients with CHARGE syndrome were well correlated: expression in the optic placode corresponded with defects such as coloboma, neural tube with mental retardation, and otic placode with ear abnormalities. The correlation between expression in the branchial arches and nasal placode with the clinical symptoms of CHARGE syndrome, however, became apparent when we encountered two unique CHARGE syndrome patients: one with a DiGeorge syndrome phenotype and the other with a Kallman syndrome phenotype. A unifying hypothesis that could explain both the DiGeorge syndrome phenotype and the Kallman syndrome phenotype in patients with CHARGE syndrome may be that the mutation in CHD7 is likely to exert its effect in the common branch of the two pathways of neural crest cells. As exemplified in CHARGE syndrome research, rare cases play a critical role in deciphering the mechanisms of human development. Close collaboration among animal researchers, epidemiologists and clinicians hopefully will enhance and maximize the scientific value of rare cases.

Original languageEnglish
Pages (from-to)12-15
Number of pages4
JournalCongenital Anomalies
Volume51
Issue number1
DOIs
Publication statusPublished - 2011 Mar

Fingerprint

CHARGE Syndrome
Research
DiGeorge Syndrome
Phenotype
Chick Embryo
Ear
Facial Asymmetry
Coloboma
Branchial Region
Mutation
Neural Tube
Neural Crest
Facial Paralysis
Facial Nerve
Human Development
Nose
Intellectual Disability
In Situ Hybridization
Research Personnel

Keywords

  • CHARGE syndrome
  • CHD7
  • Dysmorphology
  • London Dysmorphology Database
  • Methimazole embryopathy

ASJC Scopus subject areas

  • Developmental Biology
  • Pediatrics, Perinatology, and Child Health
  • Embryology

Cite this

Role of rare cases in deciphering the mechanisms of congenital anomalies : CHARGE syndrome research. / Kosaki, Kenjiro.

In: Congenital Anomalies, Vol. 51, No. 1, 03.2011, p. 12-15.

Research output: Contribution to journalArticle

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