title: Prader-Willi syndrome with a long-contiguous stretch of homozygosity not covering the critical region.
abstract: Prader-Willi syndrome is a common and complex disorder affecting multiple systems. Its main manifestations are infantile hypotonia with a poor sucking reflex, a characteristic facial appearance, mild mental retardation, hypogonadism and early-onset obesity. Prader-Willi syndrome is due to the absence of paternally expressed imprinted genes at 15q11.2-13, and 3 main mechanisms are known to be involved in its pathogenesis: paternal microdeletions, maternal uniparental disomy events, and imprinting defects. DNA methylation analysis can detect almost all individuals with Prader-Willi syndrome but is unable to distinguish between the molecular classes of the disease. Thus, additional methods are necessary to identify the molecular classes. Here, we employed chromosomal microarray analysis-single nucleotide polymorphism for diagnosis and detected a long-contiguous stretch of homozygosity on chromosome 15, which is highly predictive of maternal uniparental disomy on chromosome 15. Other methods, including fluorescence in situ hybridization, chromosomal microarray analysis-comparative genomic hybridization, genotyping and family linkage analysis, were performed for further validation. In conclusion, our study highlights the use of long-contiguous stretch of homozygosity detection for the diagnosis of Prader-Willi syndrome.
authors.affiliation: Fetal Medicine Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China fairyfareyj@sina.com.
authors.forename: Xie
authors.initials: X
authors.lastname: Yingjun
authors.affiliation: Fetal Medicine Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Yi
authors.affiliation: Fetal Medicine Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Jianzhu
authors.affiliation: Department of Neonatology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Sun
authors.initials: S
authors.lastname: Yunxia
authors.affiliation: Fetal Medicine Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yongzhen
authors.affiliation: Department of Laboratory Medicine, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Liangying
authors.affiliation: Department of Medical Genetics, Zhongshan School of Medicine and Center for Genome Research, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xiangyi
authors.affiliation: Fetal Medicine Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Qun
mesh_terms: D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D003582:Cytogenetics; D008040:Genetic Linkage; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D046228:Microarray Analysis; D020641:Polymorphism, Single Nucleotide; D011218:Prader-Willi Syndrome / Q000175:diagnosis* / Q000235:genetics*
keywords: Prader-Willi syndrome; chromosomal microarray analysis–single nucleotide polymorphism array; long-contiguous stretch of homozygosity; uniparental disomy