OBJECTIVETo determine the karyotype of a patient with Prader-Willi-like syndrome features.

METHODSChromosomal high resolution banding was carried out to analyze the karyotype of the patient, and methylation-specific PCR was used to analyze the imprinting region of chromosome 15. Subtelomeric region was screened by multiplex ligation-dependent probe amplification (MLPA), and fluorescent in situ hybridization (FISH) and real-time quantitative PCR were further performed to identify the deleted region.

RESULTSNo abnormality was discovered by high resolution karyotype analysis and methylation-specific PCR studies. MLPA analysis showed that the patient had a deletion of 1p subtelomeric area, which was confirmed by FISH analysis. The deleted region was shown within a 4.2 Mb in the distal 1p by 3 BAC FISH probes of 1p36 combined with real-time PCR technique. Family pedigree investigation showed the chromosome abnormality was de novo. Therefore, partial monosomy 1p36 was likely responsible for the mental retardation of the patient.

CONCLUSIONMolecular cytogenetic techniques should be performed to those patients with Prader-Willi-like syndrome features, to determine their karyotypes.

Child ; Chromosome Deletion ; Chromosomes, Human, Pair 1 ; genetics ; Female ; Humans ; Karyotyping ; Prader-Willi Syndrome ; genetics

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

Female ; Growth Hormone ; therapeutic use ; Humans ; Infant ; Prader-Willi Syndrome ; diagnosis ; drug therapy ; genetics

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

Growth Disorders ; drug therapy ; genetics ; Human Growth Hormone ; therapeutic use ; Humans ; Laron Syndrome ; drug therapy ; Prader-Willi Syndrome ; drug therapy

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

OBJECTIVEPrader-Willi syndrome (PWS) is a complex, multisystem disorder, which is difficult to be diagnosed based on clinical symptoms and the purpose of this study is to establish methylation-specific PCR (MS-PCR) assay for the diagnosis of PWS, and evaluate its use in clinical cases. MS-PCR assay has been developed abroad for 10 years, and it is efficient, fast, specific and sensitive but it has not yet been used in clinical diagnosis in our country.

METHODSForty-four subjects were assigned to 3 groups: normal controls (n=16), typical PWS patients (n=7) and suspected PWS patients (n=21). Genome DNA was extracted by salt fractionation method and treated with CpGemone Fast Modification Kit. Using unmodified genome DNA as system control, the modified DNA was amplified by PCR with two primer pairs (M and P), and separated by agarose gel electrophoresis.

RESULTSAll normal controls showed both 174 bp (M) and 100 bp (P) products, while all of the seven typical PWS patients demonstrated only 174 bp (M) product. In the 21 suspected patients, two cases were confirmed with PWS by MS-PCR, while others were excluded from PWS.

CONCLUSIONSMS-PCR appears to be a specific, efficient and convenient assay for the diagnosis of PWS.

Adolescent ; Child ; Child, Preschool ; DNA Methylation ; Female ; Humans ; Infant ; Male ; Polymerase Chain Reaction ; methods ; Prader-Willi Syndrome ; diagnosis ; genetics

Age Factors ; Child ; Diagnosis, Differential ; Humans ; Polymerase Chain Reaction ; Prader-Willi Syndrome ; diagnosis ; genetics ; therapy ; Prognosis ; Treatment Outcome

OBJECTIVEPrader-Willi Sydrome (PWS) is a human disorder related to genomic imprinting defect on 15q11-13. It is characterized by a series of classic features such as hypotonia, hyperphagia, obesity, osteoporosis, typical facial and body dysmorphosis, hypogonadism, mental and behaviour disorders. Our study was designed to precisely detect the microdeletions, which accounts for 65%-70% of the PWS.

METHODSPhysical and laboratory examinations were firstly performed to diagnose PWS clinically, and to discover novel clinical features. Then the patient was screened with bisulfite-specific sequencing and precisely delineated through high-density array CGH.

RESULTSWith the bisulfite-specific sequencing, the detected CpG island in the PWS critical region was found homozygously hypermethylated. Then with array CGH, a 2.22 Mb type II microdeletion was detected, covering a region from MKRN3, MAGEL2, NDN, PWRN2, PWRN1, C12orf2, SNURF-SNRPN, C/D snoRNAs, to distal of UBE3A.

CONCLUSIONSArray CGH, after the fast screening of Bisulfite-specific sequencing, is a feasible and precise method to detect microdeletions in PWS patients. A novel feature of metacarpophalangeal joint rigidity was also presented, which is the first time reported in PWS.

Base Sequence ; Chromosome Deletion ; DNA Primers ; Female ; Humans ; Infant, Newborn ; Nucleic Acid Hybridization ; Prader-Willi Syndrome ; genetics