OBJECTIVETo screen for genomic copy number variants (CNVs) in a fetus with one sibling affected with Prader-Willi syndrome using single nucleotide polymorphism (SNP) array.

METHODSThe fetus and its parents were subjected to chromosomal karyotyping and SNP array analysis.

RESULTSA 5p15.33 microdeletions was identified in the fetus and its phenotypically normal mother with a size of 344 kb (113 576 to 457 213). The father was normal for both testing. Analysis of literature and CNVs database indicated the above CNV to be variant of unclear significance. The couple decided to continue with the pregnancy and gave birth to a healthy boy at full-term. No abnormalities were found during the follow-up.

CONCLUSIONThis study may provide further data for the phenotype-genotype correlation of 5p15.33 microdeletion, which differs from Cri du Chat syndrome.

Adult ; Chromosome Deletion ; Chromosomes, Human, Pair 5 ; genetics ; DNA Copy Number Variations ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Male ; Prader-Willi Syndrome ; diagnosis ; embryology ; genetics ; Pregnancy ; Prenatal Diagnosis

This article reports the clinical features and endocrine and metabolic features of 4 children with Prader-Willi syndrome (PWS). All the patients were female and aged 6-12 years at diagnosis. All of them had clinical manifestations of obesity, unusual facies, developmental retardation, and intellectual disability. Genetic detection showed that 2 patients had paternal deletion of the 15q11.2-q13 region, one patient had maternal autodiploid in the 15q11.2-q13 region, and one patient had no abnormality in the 15q11.2-q13 region. All patients had varying degrees of endocrine and metabolic disorders: 2 patients had short stature, among whom one had delayed appearance of secondary sex characteristics and the other one had type 2 diabetes; one patient had insulin resistance and no mammary gland development; one patient had a body height of P-Pand precocious puberty. Patients with PWS have various endocrine disorders, so long-term endocrine follow-up and management is very important.
Child ; Child, Preschool ; Endocrine Glands ; physiopathology ; Female ; Glucose Tolerance Test ; Humans ; Prader-Willi Syndrome ; genetics ; physiopathology

The Prader-Willi syndrome (PWS) is a human imprinting disorder resulting from genomic alterations that inactivate imprinted, paternally expressed genes in human chromosome region 15q11-q13. This genetic condition appears to be a contiguous gene syndrome caused by the loss of at least 2 of a number of genes expressed exclusively from the paternal allele, including SNRPN, MKRN3, MAGEL2, NDN and several snoRNAs, but it is not yet well known which specific genes in this region are associated with this syndrome. Prader-Will-Like syndrome (PWLS) share features of the PWS phenotype and the gene functions disrupted in PWLS are likely to lie in genetic pathways that are important for the development of PWS phenotype. However, the genetic basis of these rare disorders differs and the absence of a correct diagnosis may worsen the prognosis of these individuals due to the endocrine-metabolic malfunctioning associated with the PWS. Therefore, clinicians face a challenge in determining when to request the specific molecular test used to identify patients with classical PWS because the signs and symptoms of PWS are common to other syndromes such as PWLS. This review aims to provide an overview of current knowledge relating to the genetics of PWS and PWLS, with an emphasis on identification of patients that may benefit from further investigation and genetic screening.
Alleles ; Chromosomes, Human ; Diagnosis ; Genetic Testing ; Genetics* ; Humans ; Phenotype ; Prader-Willi Syndrome* ; Prognosis ; RNA, Small Nucleolar ; snRNP Core Proteins

The Prader-Willi syndrome (PWS) is a human imprinting disorder resulting from genomic alterations that inactivate imprinted, paternally expressed genes in human chromosome region 15q11-q13. This genetic condition appears to be a contiguous gene syndrome caused by the loss of at least 2 of a number of genes expressed exclusively from the paternal allele, including SNRPN, MKRN3, MAGEL2, NDN and several snoRNAs, but it is not yet well known which specific genes in this region are associated with this syndrome. Prader-Will-Like syndrome (PWLS) share features of the PWS phenotype and the gene functions disrupted in PWLS are likely to lie in genetic pathways that are important for the development of PWS phenotype. However, the genetic basis of these rare disorders differs and the absence of a correct diagnosis may worsen the prognosis of these individuals due to the endocrine-metabolic malfunctioning associated with the PWS. Therefore, clinicians face a challenge in determining when to request the specific molecular test used to identify patients with classical PWS because the signs and symptoms of PWS are common to other syndromes such as PWLS. This review aims to provide an overview of current knowledge relating to the genetics of PWS and PWLS, with an emphasis on identification of patients that may benefit from further investigation and genetic screening.
Alleles ; Chromosomes, Human ; Diagnosis ; Genetic Testing ; Genetics* ; Humans ; Phenotype ; Prader-Willi Syndrome* ; Prognosis ; RNA, Small Nucleolar ; snRNP Core Proteins

PURPOSE: Floppy infant, or congenital hypotonia, is caused by various diseases, such as genomic disorders, diseases involving the central or peripheral nervous system, musculoskeletal diseases, and metabolic disorders. We describe here the clinical aspects and the final diagnosis of infants with hypotonia recently diagnosed in a single, tertiary-care hospital in Korea. METHODS: All of the infants evaluated for generalized hypotonia between 2008 and 2012 at Asan Medical Center Children's Hospital were included in our study. The demographic data, physical examination upon initial presentation, the diagnostic tests and results, and the final diagnosis were retrospectively reviewed. RESULTS: A total of 128 infants (68 males, 60 females) were included in the study, and the mean patient age at the time of the diagnosis of hypotonia was 4.8 months. Etiological diagnosis was possible in 80 (62.5%) of the 128 patients, and 57 (44.5%) patients were confirmed by genetic testing. Fifteen patients (11.7%) were categorized as having central nervous system disorders, and 34 (26.6%) patients were diagnosed as having other genomic disorders such as Prader-Willi syndrome (n=17). Disease involving muscle and the peripheral nervous system was detected in 16 (12.5%) patients. Five patients were diagnosed with other skeletal disorders, and metabolic disease was detected in 10 (7.8%) patients. CONCLUSION: With the recent advances in diagnostic tools, including genetic testing, many of the patients with hypotonia can be correctly diagnosed. These data can give practical clues regarding the optimal diagnostic approaches for treating floppy infants in the clinics.
Central Nervous System Diseases ; Chungcheongnam-do ; Diagnosis ; Diagnostic Tests, Routine ; Genetic Testing ; Genetics ; Humans ; Infant* ; Korea ; Male ; Metabolic Diseases ; Muscle Hypotonia ; Musculoskeletal Diseases ; Peripheral Nervous System ; Physical Examination ; Prader-Willi Syndrome ; Retrospective Studies

OBJECTIVETo investigate the genotype-phenotype correlation in patients with Angelman syndrome/Prader-Willi syndrome (AS/PWS) and assess the application value of high-resolution single nucleotide polymorphism microarrays (SNP array) for such diseases.

METHODSTwelve AS/PWS patients were diagnosed through SNP array, fluorescence in situ hybridization (FISH) and karyotype analysis. Clinical characteristics were analyzed.

RESULTSDeletions ranging from 4.8 Mb to 7.0 Mb on chromosome 15q11.2-13 were detected in 11 patients. Uniparental disomy (UPD) was detected in only 1 patient. Patients with deletions could be divided into 2 groups, including 7 cases with class I and 4 with class II. The two groups however had no significant phenotypic difference. The UPD patient had relatively better development and language ability. Deletions of 6 patients were confirmed by FISH to be of de novo in origin. The risk to their sibs was determined to be less than 1%.

CONCLUSIONThe phenotypic differences between AS/PWS patients with class I and class II deletion need to be further studied. SNP array is useful in detecting and distinguishing of patients with deletion or UPD. This method may be applied for studying the genotype-phenotype association and the mechanism underlying AS/PWS.

Angelman Syndrome ; diagnosis ; genetics ; Child, Preschool ; Chromosome Deletion ; Female ; Genotype ; Humans ; Infant ; Karyotyping ; Male ; Phenotype ; Polymorphism, Single Nucleotide ; Prader-Willi Syndrome ; diagnosis ; genetics

Biomarkers ; blood ; Humans ; Infant, Newborn ; Magnetic Resonance Imaging ; Male ; Prader-Willi Syndrome ; diagnosis ; genetics ; pathology ; therapy

OBJECTIVEPrader-Willi syndrome (PWS) with different pathogenesis has different clinical manifestations, prognosis and genetic risks. Pathogenesis of the disease cannot be explained by conventional diagnostic method MS-PCR. This study employed methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) for the diagnosis of PWS in order to explore the role of this method in the diagnosis and assessment of pathogenesis of PWS.

METHODSA system antithetical method was employed. Peripheral blood samples were collected from 30 children for MS-PCR. Of the 30 children, 16 were diagnosed with PWS by MS-PCR and the other 14 showed negative MS-PCR. MS-MLPA kit Me028 was used to detect DNA extracted from the 30 samples.

RESULTSThe results showed by MS-MLPA and MS-PCR were identical. MS-MLPA demonstrated that 4 cases were maternal uniparental disomy and 12 cases were paternal dfeletion in 15q11-q13 region.

CONCLUSIONSMS-MLPA is a reliable method of genetic testing for PWS which can distinguish pathogenesis of PWS.

Child, Preschool ; DNA Methylation ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Nucleic Acid Amplification Techniques ; methods ; Polymerase Chain Reaction ; Prader-Willi Syndrome ; diagnosis ; genetics

OBJECTIVETo definite the etiopathogenisis by carrying out the genome-wide copy number variation analysis for a suspect patient with Prader-Willi syndrome.

METHODSThe peripheral blood was collected from the patient who was diagnosed as having Prader-Willi syndrome, as well as his parents for conventional cytogenetic G-banding and high resolution chromosome assay. Genomic DNA of the child patient was extracted from the blood to perform the genome-wide copy number variation analysis.

RESULTSThere was a heterozygosis deletion of a 5Mb region in chromosome 15q11.2-q13.1 by the genome-wide copy number variation analysis, but no abnormality was observed in high resolution chromosome assay in the child patient and his parents. Baylay and Gesell developmental scale was assessed regularly; the results suggested that the IQ of the child patient was 60-70, according with the clinical feature of Prader-Willi syndrome.

CONCLUSIONThe heterozygosis deletion in chromosome 15q11.2-q13.1 is the cause of Prader-Willi syndrome in this family. Further molecular genetics detection can make up for the insufficiency in cytogenetics methods, when no abnormality is observed at the level of cytogenetics in patients with Prader-Willi syndrome.

Cytogenetic Analysis ; DNA Copy Number Variations ; genetics ; Female ; Follow-Up Studies ; Genome, Human ; genetics ; Humans ; Infant, Newborn ; Male ; Prader-Willi Syndrome ; genetics ; pathology ; physiopathology

OBJECTIVETo diagnose and detect the molecular defect in a suspected patient with Prader-Willi syndrome.

METHODSGenetic diagnosis and molecular genetic analysis were performed by using chromosome karyotype analysis, methylation-specific PCR (MS-PCR), and linkage analysis using short tandem repeat (STR).

RESULTSThe karyotype of the patient was 45, XX, der(5), t(5;15)(q35;q13), -15, and the parents were 46, XY and 46, XX, respectively, implying that the unbalanced translocation t(5;15) in the patient was de novo. Furthermore, MS-PCR and STR linkage analysis confirmed that the patient's 15q11-13 deletion was resulted from unbalanced translocation on paternal chromosome 15.

CONCLUSIONGenetic analysis should be applied in suspected patients with Prader-Willi syndrome to confirm the diagnosis. Cytogenetic and molecular techniques would be helpful in clinical diagnosis, genetic counseling and prenatal diagnosis.

Chromosomes, Human, Pair 15 ; genetics ; Chromosomes, Human, Pair 5 ; genetics ; DNA Methylation ; Female ; Genetic Linkage ; Humans ; Infant ; Karyotyping ; Male ; Microsatellite Repeats ; genetics ; Polymerase Chain Reaction ; Prader-Willi Syndrome ; diagnosis ; genetics ; pathology ; physiopathology ; Translocation, Genetic ; genetics