Clinical Application of an Innovative Multiplex-Fluorescent-Labeled STRs Assay for Prader-Willi Syndrome and Angelman Syndrome

Abstract

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two clinically distinct neurodevelopmental disorders caused by absence of paternally or maternally expressed imprinted genes on chr15q11.2-q13.3. Three mechanisms are known to be involved in the pathogenesis: microdeletions, uniparental disomy (UPD) and imprinting defects. Both disorders are difficult to be definitely diagnosed at early age if no available molecular cytogenetic tests. In this study, we identified 5 AS patients with the maternal deletion and 26 PWS patients with paternal deletion on chr15q11-q13 by using an innovative multiplex-fluorescent-labeled short tandem repeats (STRs) assay based on linkage analysis, and validated by the methylation-specific PCR and array comparative genomic hybridization techniques. More interesting, one of these PWS patients was confirmed as maternal uniparental isodisomy by the STR linkage analysis. The phenotypic and genotypic characteristics of these individuals were also presented. Our results indicate that the new linkage analysis is much faster and easier for large-scale screening deletion and uniparental disomy, thus providing a valuable method for early diagnosis of PWS/AS patients, which is critical for genetic diagnosis, management and improvement of prognosis.

Uniparental Disomy of Chromosome 15 in Two Cases by Chromosome Microarray: A Lesson Worth Thinking

“…Both cases were finally identified by a multiplex-fluorescence-labeled STR assay which was developed and described previously for a rapid and economic detection of deletion or UPD 15 based on linkage analysis [Zhang et al, 2016]. STR linkage analysis traces the transmission of chromosome 15 from each parent to the child by using informative STR markers in order to determine whether the proband demonstrates normal biparental inheritance, only maternal markers (PWS), or only paternal markers (AS).…”

“…The experimental procedures were described in our previous study [Zhang et al, 2016]. GENE-MAPPER software (Applied Biosystems) was used for data collection and allele sizing.…”

The spectrum of microdeletian syndromes at the hospital of Lithuanian university of health sciences

“…Prader-Willi syndrome (PWS) has a prevalence of 1/15000 to 1/30000 (LANDAU et al, 2016). The syndrome detection age is ranging from newborn to 15 years and even in adulthood (ZHANG et al, 2016). The major criteria list of Prader-Willi syndrome includes neonatal and infantile central hypotonia with poor suck reflex, feeding problems during infancy, excessive weight gain, dysmorphic face features which involves narrow face and almond shape eyes, hypogonadism, hyperphagia, global developmental delay and mental retardation.…”

“…The frequency of Angelman syndrome (AS) is from 1 in 10000 to 1 in 20000 newborns (PANDA et al, 2013). The age when Angelman syndrome was detected varies from 2 months to 12 years (BAI et al, 2010;DUCA et al, 2013;ZHANG et al, 2016). The syndrome has three categories of consensus symptoms criteria: consistent features (100% of the patients), frequent features (>80% of the patients) and associated features (20-80% of the patients).…”

Genetic testing for Prader-Willi syndrome and Angelman syndrome in the clinical practice of Guangdong Province, China

“…105,830) are clinically distinct neurogenetic disorders with multiple phenotypic manifestations. PWS patients present with neonatal hypotonia, poor sucking and weak cry in the postnatal period, delayed psychomotor development and hyperphagia in early childhood, severe obesity, short stature and hypogonadism in adolescents [1]; The initial symptoms of AS overlap with a lot of other disorders, and more characteristic features present later in childhood, including microcephaly, severe developmental delay, gait ataxia and/or tremulousness of the limbs, seizures, absent or severely limited speech, and a unique behavior with happy demeanor [2]. Each syndrome occurs with an estimated prevalence of 1:15,000–1:25,000 live births [3].…”