CHARGE syndrome due to deletion of region upstream of CHD7 gene START codon

Research output: Contribution to journalArticle

Abstract

Background: CHARGE syndrome is an autosomal dominant disorder, characterized by ocular Coloboma, congenital Heart defects, choanal Atresia, Retardation, Genital anomalies and Ear anomalies. Over 90 % of typical CHARGE patients are mutated in the CHD7 gene, 65 %-70 % of the cases for all typical and suspected cases combined. The gene encoding for a protein involved in chromatin organization. The mutational spectrum include nonsense, frameshift, splice site, and missense mutations. Large deletions and genomic rearrangements are rare. Case presentation: We report here on a 5.9 years old male of Moroccan origin displaying classic clinical features of CHARGE syndrome. Using CGH array and NGS analysis we detected a microdeletion (184 kb) involving the promoter region and exon 1 of CHD7 gene and the flanking RAB2 gene. Conclusion: The present observation suggests that deletion limited to the regulatory region of CHD7 is sufficient to cause the full blown CHARGE phenotype. Different size of deletions can result in different phenotypes, ranging from a milder to severe CHARGE syndrome; this is based on a combination of major and minor diagnostic characteristics, therefore to a more variable clinical features, likely due to the additive effect of other genetic imbalances. MLPA and CGH techniques should be considered in the diagnostic protocol of individuals with a clinical suspect of CHARGE syndrome

Original languageEnglish
Article number78
JournalBMC Medical Genetics
Volume16
Issue number1
DOIs
Publication statusPublished - Sep 3 2015

Fingerprint

CHARGE Syndrome
Codon
Genes
Choanal Atresia
Coloboma
Phenotype
Congenital Heart Defects
Nucleic Acid Regulatory Sequences
Missense Mutation
Genetic Promoter Regions
Chromatin
Ear
Exons
Proteins

Keywords

  • CGH array
  • CHARGE syndrome
  • CHD7 gene
  • deletion
  • Next Generation Sequencing

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

CHARGE syndrome due to deletion of region upstream of CHD7 gene START codon. / Pisaneschi, Elisa; Sirleto, Pietro; Lepri, Francesca Romana; Genovese, Silvia; Dentici, Maria Lisa; Petrocchi, Stefano; Angioni, Adriano; Digilio, Maria Cristina; Dallapiccola, Bruno.

In: BMC Medical Genetics, Vol. 16, No. 1, 78, 03.09.2015.

Research output: Contribution to journalArticle

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