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

• Published in: American journal of medical genetics. Part A 2011-10, Vol.155 (10), p.2584-2588
• Main Authors: Tohyama, Jun, Yamamoto, Toshiyuki, Hosoki, Kana, Nagasaki, Keisuke, Akasaka, Noriyuki, Ohashi, Tsukasa, Kobayashi, Yu, Saitoh, Shinji
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; chromosome 14; Chromosomes; Chromosomes, Human, Pair 14 - genetics; Comparative Genomic Hybridization; copy number; Cytogenetic Analysis; DNA methylation; DNA microarrays; Epilepsy; Female; Fluorescence in situ hybridization; Forkhead Transcription Factors - genetics; FOXG1; Foxg1 protein; Gene Duplication - genetics; genomics; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Hybridization analysis; In Situ Hybridization, Fluorescence; Infant; Infants; Karyotyping; maternal uniparental disomy; Medical genetics; Medical sciences; Microsatellite Repeats - genetics; Microsatellites; mosaic duplication; Mosaicism; Mosaics; Nerve Tissue Proteins - genetics; Nervous system (semeiology, syndromes); Neurology; Seizures; Spasms, Infantile - genetics; Spasms, Infantile - pathology; Supernumerary; supernumerary marker chromosome; uniparental disomy; Uniparental Disomy - genetics; West syndrome
• ISSN: 1552-4825; 1552-4833; 1552-4833
• DOI: 10.1002/ajmg.a.34224

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. © 2011 Wiley‐Liss, Inc.