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

Abstract

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.

• Authors: Jun Tohyama, Toshiyuki Yamamoto, Kana Hosoki, Keisuke Nagasaki, Noriyuki Akasaka, Tsukasa Ohashi, Yu Kobayashi, Shinji Saitoh
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 155A Issue 10 Pg. 2584-8 (Oct 2011) ISSN: 1552-4833 [Electronic] United States
• PMID: 21910242 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2011 Wiley-Liss, Inc.

Chemical References

• FOXG1 protein, human
• Forkhead Transcription Factors
• Nerve Tissue Proteins

Topics

• Chromosomes, Human, Pair 14 (genetics)
• Comparative Genomic Hybridization
• Cytogenetic Analysis
• Female
• Forkhead Transcription Factors (genetics)
• Gene Duplication (genetics)
• Humans
• In Situ Hybridization, Fluorescence
• Infant
• Karyotyping
• Microsatellite Repeats (genetics)
• Mosaicism
• Nerve Tissue Proteins (genetics)
• Spasms, Infantile (genetics, pathology)
• Uniparental Disomy (genetics)