Prader-Willi syndrome (PWS) is a neurobehavioral disorder manifested by infantile hypotonia and feeding difficulties in infancy, followed by morbid obesity secondary to hyperphagia. It is caused by deficiency of paternally expressed transcript(s) within the human chromosome region 15q11.2. PWS patients harboring balanced chromosomal translocations with breakpoints within small nuclear ribonucleoprotein polypeptide N (SNRPN) have provided indirect evidence for a role for the imprinted C/D box containing small nucleolar RNA (snoRNA) genes encoded downstream of SNRPN. In addition, recently published data provide strong evidence in support of a role for the snoRNA SNORD116 cluster (HBII-85) in PWS etiology. In this study, we performed detailed phenotypic, cytogenetic, and molecular analyses including chromosome analysis, array comparative genomic hybridization (array CGH), expression studies, and single-nucleotide polymorphism (SNP) genotyping for parent-of-origin determination of the 15q11.2 microdeletion on an 11-year-old child expressing the major components of the PWS phenotype. This child had an B236.29 kb microdeletion at 15q11.2 within the larger Prader-Willi/Angelman syndrome critical region that included the SNORD116 cluster of snoRNAs. Analysis of SNP genotypes in proband and mother provided evidence in support of the deletion being on the paternal chromosome 15. This child also met most of the major PWS diagnostic criteria including infantile hypotonia, early-onset morbid obesity, and hypogonadism. Identification and characterization of this case provide unequivocal evidence for a critical role for the SNORD116 snoRNA molecules in PWS pathogenesis. Array CGH testing for genomic copy-number changes in cases with complex phenotypes is proving to be invaluable in detecting novel alterations and enabling better genotype-phenotype correlations. European Journal of Human Genetics (2010Genetics ( ) 18, 1196Genetics ( -1201 doi:10.1038/ejhg.2010; published online 30 June 2010Keywords: Prader-Willi syndrome; snoRNA; microdeletion; array CGH INTRODUCTION Prader-Willi syndrome (PWS; MIM 176270) is a neurobehavioral disorder caused by the lack of paternal expression of imprinted genes in the human chromosome region 15q11.2q13. PWS manifests as infantile hypotonia, genital hypoplasia, and neonatal feeding difficulties, followed by hyperphagia leading to profound obesity in early childhood and into adulthood. 1,2 Large interstitial deletions of B6-6.8 Mb at 15q11.2q13 of paternal origin are the cause in over 70% of cases. The majority of the remaining cases have maternal uniparental disomy (UPD) 15, and a small percentage have imprinting defects. Deletions at 15q11.2q13 of maternal origin result in Angelman syndrome (MIM 105830). Identification and characterization of the recurrent deletion breakpoints have revealed low-copy repeat-mediated nonallelic homologous recombination as the unifying mechanism for the common deletions and duplications across this interval. 3,4 A number of paternally expressed genes mapping with...

Whole-genome prenatal aCGH detected clinically significant submicroscopic chromosome abnormalities in addition to chromosome abnormalities that could be identified by concurrent karyotyping without an increase in unclear results or benign CNVs compared to targeted aCGH.

The chance of detecting a chromosome abnormality in a prenatal population that has already been screened by routine cytogenetics is approximately 1.3%. However, given that many of the abnormal array results in the neonatal population were among those with dysmorphic features as the primary indication for testing, which are not easily identifiable by ultrasound, offering prenatal testing by aCGH to a wider population would likely result in a higher detection rate.

Objective To develop a novel, rapid prenatal assay for pregnancies with high likelihood of normal karyotypes, using BACs‐on‐Beads™ technology, a suspension array‐based multiplex assay that employs Luminex® xMAP® technology, for the detection of gains and losses in chromosomal DNA. Methods Fifteen relatively common microdeletions were selected that are not detectable, or may be missed, by karyotyping and usually do not present with abnormal ultrasound findings. Chromosomes 13, 18, 21, X, and Y were included. We validated the assay with 430 samples. Results All microdeletions and aneuploidies were correctly identified, except for a 69,XXX incorrectly identified as a normal female and a male with ∼20% maternal cell contamination (MCC) that could not be distinguished from 69,XXY. MCC became apparent at 20 to 30%. Mosaicism was identified at 30 to 35% abnormal cells. Conclusion We have developed an alternative to fluorescence in situ hybridization (FISH) aneuploidy screening and microarray analysis in otherwise normal pregnancies undergoing invasive testing. We demonstrated that the assay will detect all microdeletions and aneuploidies of regions covered on the assay. We developed analytical software that displays results for well‐characterized syndromes but not abnormalities of unclear clinical significance. This assay is likely to be preferred by women seeking testing beyond routine karyotyping but who desire more information than provided by aneuploidy FISH. Copyright © 2011 John Wiley & Sons, Ltd.

The mechanisms underlying cervical insufficiency, a cause of spontaneous second-trimester abortion and early preterm birth, remain poorly understood. There is, however, evidence that amniotic fluid (AF) infection is a key factor in pregnancy outcomes and postoperative complications. This study was an attempt to determine the frequency and clinical importance of intraamniotic inflammation in 52 patients with acute cervical insufficiency, defined as cervical dilation of 1.5 cm or more. The patients, seen at 17 to 29 weeks' gestation, had intact membranes, and were not having regular uterine connections. AF samples were cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and assayed for matrix metalloproteinase-8; a level exceeding 23 ng/mL was deemed to represent the presence of intraamniotic inflammation.Intraamniotic inflammation was present in 42 of the 52 study patients (81%), and 4 patients (8%) had a positive AF culture. All culture-positive patients had intraamniotic inflammation. Among patients with intraamniotic inflammation but not AF infection, preterm delivery occurred within 7 days in 50%, and delivery before 34 weeks gestation, in 84%. More than half of newborn infants (55%) whose mothers had inflammation but not infection died within 24 hours of birth. The presence of intraamniotic inflammation was associated with a shorter interval between amniocentesis to delivery. The risk of an adverse pregnancy outcome did not differ between patients with intraamniotic inflammation and a negative culture on the one hand and, on the other, between those with confirmed AF infection. Fetal morbidity was not substantially altered by cesarean delivery.Whether the AF is culture-positive, a large majority of patients with acute cervical insufficiency have intraamniotic inflammation, and this is a risk factor for both preterm delivery and adverse pregnancy outcomes. ABSTRACTShoulder dystocia is an uncommon event that is largely unpredictable, and that may cause serious morbidity in both the mother and infant. Brachial plexus injury may be worsened by inappropriate treatment. This retrospective observational study compared the management and outcome of births complicated by shoulder dystocia before and after introducing 1 day of training that utilized a prototype shoulder dystocia training mannequin. Training included risk factors, recognition, documentation, helpful maneuvers, and a simulated shoulder dystocia scenario.A total of 15,908 pretraining births were compared with 13,117 taking place after the introduction of training. Rates of shoulder dystocia were similar: 2.04% in the pretraining group and 2.00% in the posttraining group. Before training, none of the several maneuvers recommended for the resolution of shoulder dystocia (including McRoberts' position, suprapubic pressure, internal rotation, delivery of the posterior arm, and the All-Fours-Maneuvers) were utilized in half or more of the affected infants. After training, in contrast, at least 1 of the recommended maneuvers was utilized in mor...