West syndrome associated with mosaic duplication of FOXG1 in a patient with maternal uniparental disomy of chromosome 14

Department of Pediatrics, Epilepsy Center, Nishi-Niigata Chuo National Hospital, Japan.
American Journal of Medical Genetics Part A (Impact Factor: 2.16). 10/2011; 155A(10):2584-8. DOI: 10.1002/ajmg.a.34224
Source: PubMed


FOXG1 on chromosome 14 has recently been suggested as a dosage-sensitive gene. Duplication of this gene could cause severe epilepsy and developmental delay, including infantile spasms. Here, we report on a female patient diagnosed with maternal uniparental disomy of chromosome 14 and West syndrome who carried a small supernumerary marker chromosome. A chromosomal analysis revealed mosaicism of 47,XX, + mar[8]/46,XX[18]. Spectral karyotyping multicolor fluorescence in situ hybridization analysis confirmed that the marker chromosome was derived from chromosome 14. A DNA methylation test at MEG3 in 14q32.2 and microsatellite analysis using polymorphic markers on chromosome 14 confirmed that the patient had maternal uniparental disomy 14 as well as a mosaic small marker chromosome of paternal origin containing the proximal long arm of chromosome 14. Microarray-based comparative genomic hybridization analysis conclusively defined the region of the gain of genomic copy numbers at 14q11.2-q12, encompassing FOXG1. The results of the analyses of our patient provide further evidence that not only duplication but also a small increase in the dosage of FOXG1 could cause infantile spasms.

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    • "Recently, FOXG1 was reported to be a dose-sensitive gene whose duplication could result in severe epilepsy, infantile spasms and developmental delay [Yeung et al., 2009; Brunetti-Pierri et al., 2011], while its deletion could cause seizures, but not infantile spasms [Tohyama et al., 2011]. "
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    • "We have identified known causative CNVs in three patients with isolated epilepsy and seven patients with epilepsy and other neurodevelopmental abnormalities (Table I). A number of studies have suggested that increased dosage of FOXG1 mapping to chromosome 14q12 is pathogenic for developmental delay, cognitive impairment with speech delay, and epilepsy [Yeung et al., 2009; Brunetti-Pierri et al., 2011; Paciorkowski et al., 2011; Striano et al., 2011; Tohyama et al., 2011]. However, recently, Amor et al. [2012] reported a familial case of an $88 kb duplication in 14q12, encompassing FOXG1, associated only with isolated hemifacial microsomia . "
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