Exon copy number alterations of the CHD7 gene are not a major cause of CHARGE syndrome and CHARGE-like syndrome

Department of Genetics, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
European Journal of Medical Genetics (Impact Factor: 1.47). 05/2008; 51(5):417-25. DOI: 10.1016/j.ejmg.2008.03.003
Source: PubMed


CHARGE syndrome is a multiple congenital anomaly syndrome caused by mutations in the CHD7 gene. Mutations in this gene are found in 60-70% of patients suspected of having CHARGE syndrome. However, if only typical CHARGE patients are taken into account, mutations in the CHD7 gene are found in over 90% of cases. The remaining 10% might be caused by hitherto undetected alterations of the CHD7 gene, including whole exon duplications and deletions that are missed by the currently used diagnostic procedures. Therefore we looked for these kinds of alterations by multiplex ligation-dependent probe amplification in 54 patients suspected of having CHARGE syndrome without a CHD7 mutation. In one patient a partial deletion of the CHD7 gene (exons 13-38) was identified, while in the other patients no abnormalities were found. The frequency of exon deletions in our cohort was 1.9% (1/54) and 5.6% (1/18) in all patients and in typical CHARGE patients, respectively. We conclude that exon copy number alterations of the CHD7 gene are not a major cause of CHARGE and CHARGE-like syndrome.

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    • "t al. [2008]); wg = whole gene; 0 = not mentioned in the online database. a Gennery et al., 2008. b Writzl et al., 2007. c Inoue et al., 2010. d Wincent et al., 2008. e Kaliakatsos et al., 2010. f Vuorela et al., 2007. g Vuorela et al., 2008. h Van de Laar et al., 2007. i Jongmans et al., 2006. j Hoover-Fong et al., 2009. k Vissers et al., 2004. l Bergman et al., 2011a. m Sanka et al., 2007. n Randall et al., 2009. o Chopra et al., 2008. * Atresia or stenosis of choanae. ** Only if necessitating tube feeding."
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    • "CHD7 analysis was performed as previously described [Jongmans et al., 2006] and multiplex ligation-dependent probe amplification (MLPA) was performed if CHD7 sequence analysis did not identify a mutation [Bergman et al., 2008]. The GenBank accession number NM_017780.2 was used as reference sequence for the CHD7 gene. "
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    • "Seventeen families with multiple affected members due to a segregating CHD7 mutation have been reported to date [Bergman et al., 2011b; Delahaye et al., 2007; Jongmans et al., 2006, 2008; Lalani et al., 2006; Pauli et al., 2009; Vuorela et al., 2008; Wincent et al., 2008]. In addition, we identified a presumed pathogenic missense mutation (c.6221T>C; p.Leu2074Pro) in two sisters with KS, whose clinical features were previously reported by Levy and Knudtzon (1993). "
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