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


METHODS
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.


CONCLUSIONS
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.
Medical Genetics Laboratory, Bambino Gesù Paediatric Hospital, IRCCS, Rome, Italy. elisa.pisaneschi@opbg.net.|Bambino Gesù Children Hospital, Molecular Genetics Laboratory, Viale di San Paolo 15, 00146, Rome, Italy. elisa.pisaneschi@opbg.net.
Elisa
E
Pisaneschi
Medical Genetics Laboratory, Bambino Gesù Paediatric Hospital, IRCCS, Rome, Italy. pietro.sirleto@opbg.net.
Pietro
P
Sirleto
Medical Genetics Laboratory, Bambino Gesù Paediatric Hospital, IRCCS, Rome, Italy. francescaromana.lepri@opbg.net.
Francesca Romana
FR
Lepri
Medical Genetics Laboratory, Bambino Gesù Paediatric Hospital, IRCCS, Rome, Italy. silvia.genovese@opbg.net.
Silvia
S
Genovese
Scientific Directorate, Bambino Gesù Paediatric Hospital, IRCCS, Rome, Italy. marialisa.dentici@opbg.net.
Maria Lisa
ML
Dentici
Medical Genetics Laboratory, Bambino Gesù Paediatric Hospital, IRCCS, Rome, Italy. stefano.petrocchi@opbg.net.
Stefano
S
Petrocchi
Medical Genetics Laboratory, Bambino Gesù Paediatric Hospital, IRCCS, Rome, Italy. adriano.angioni@opbg.net.
Adriano
A
Angioni
Medical Genetics, Bambino Gesù Paediatric Hospital, IRCCS, Rome, Italy. mariacristina.digilio@opbg.net.
Maria Cristina
MC
Digilio
Scientific Directorate, Bambino Gesù Paediatric Hospital, IRCCS, Rome, Italy. bruno.dallapiccola@opbg.net.
Bruno
B
Dallapiccola
D001483:Base Sequence; D058747:CHARGE Syndrome / Q000235:genetics* / Q000473:pathology; D002675:Child, Preschool; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009018:Morocco; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D017422:Sequence Analysis, DNA
D004268:DNA-Binding Proteins; D004265:DNA Helicases; C491434:CHD7 protein, human