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/46,XX. 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.
"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]. "
[Show abstract][Hide abstract] ABSTRACT: Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes, generally equal in size or smaller than a chromosome 20 of the same metaphase spread. Most of them are unexpectedly detected in routine karyotype analyses, and it is usually not easy to correlate them with a specific clinical picture. A small group of sSMCs is derived from more than one chromosome, called complex sSMCs. Here, we report on a patient with a de novo complex sSMC, derived from chromosomes 8 and 14. Banding karyotype analysis, multiplex ligation-dependent probe amplification (MLPA), single nucleotide polymorphism (SNP)-based array, and fluorescence in situ hybridization (FISH) were performed to investigate its origin. Array and FISH analyses revealed a der(14)t(8;14)(p23.2;q22.1)dn. The propositus presents some clinical features commonly found in patients with partial duplication or triplication of 8p and 14q. This is the first report describing a patient with a congenital der(14)t(8;14)(p23.2;q22.1)dn sSMC.
Cytogenetic and Genome Research 03/2013; 139(4). DOI:10.1159/000348743 · 1.56 Impact Factor
"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.  reported a familial case of an $88 kb duplication in 14q12, encompassing FOXG1, associated only with isolated hemifacial microsomia . "
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