A simple and effective approach for detecting maternal cell contamination in molecular prenatal diagnosis

The presence of maternal cells in fetal samples constitutes a serious potential source for prenatal misdiagnosis, Here we present our approach for detecting maternal cell contamination (MCC) at prenatal diagnosis for eight monogenic disorders (autosomal recessive: beta-thalassaemia, sickle-cell anaemia, cystic fibrosis, prelingual deafness’ autosomal dominant: achondroplasia, Huntington disease, myotonic dystrophy. neurofibromatosis type 1: X-linked: spinobulbar muscular atrophy). Our aim was to apply a simple and low-cost approach. which would easily and accurately provide information on the fetal tissue MCC status. MCC testing was applied to cases of recessive inheritance adhere the primary mutation screening of the fetus revealed the presence of the maternal mutation. to cases concerning dominant inheritance and to cases of multiple gestation, The potential presence of maternal cells was determined by the amplification of the 3’-HVR/APO B. D1S80, THO1 and VNTRI of vWf polymorphic loci, which have previously demonstrated high heterozygosity in Caucasians. Among 135 prenatal diagnoses. 44 finally needed to be tested for MCC (32.6%). MCC was detected in four cases, where DNA was isolated directly from chorionic villi samples (CVS). and in one case with DNA isolated directly from amniotic fluid (AF). In almost 90%, of cases a simple test of one polymorphic locus provided sufficient information about MCC. The choice of the appropriate locus is therefore essential, while the simultaneous screening of both parents provides the means for distinguishing non-informative sites about MCC. Copyright (C) 2002 John Wiley Sons, Ltd

Cranioectodermal dysplasia: A probable ciliopathy

Cranioectodermal dysplasia (CED), also known as Sensenbrenner syndrome, is a rare autosomal recessive genetic disorder characterized by typical craniofacial, skeletal and ectodermal defects, and tubulointerstitial nephritis leading to early end-stage renal failure. We report on a new familial case of a 9-year-old patient and two fetuses of 23 and 19 weeks of gestation respectively. Hypohidrosis was an additional ectodermal finding is the patient with CED. Postmortem findings in the two fetuses included acromesomelic shortening, craniofacial characteristics with absence of craniosynostosis, small kidneys with tubular and glomerular microscopic cysts, persistent ductal plate with portal fibrosis in the liver, small adrenals and roughly unremarkable histopathology of the physeal growth plate. Posterior fossa anomalies were additional findings in this patient and included an enlarged cisterna magna and a posterior fossa cyst. The above findings, in association with renal cysts, persistent ductal plate and portal fibrosis, introduce CED, a nonlethal genetic skeletal disorder of yet unknown molecular origin, as a possible member of the expanding group of ciliopathies. © 2009 Wiley-Liss, Inc

Pathologic, radiographic and molecular findings in three fetuses diagnosed with HEM/Greenberg skeletal dysplasia

Background: Greenberg skeletal dysplasia is a very rare, autosomal recessive, in utero, lethal chondrodystrophy for which only eight index cases of diverse ethnic origin have been reported so far. The defect is associated with a defect in cholesterol biosynthesis and due to mutations in the gene encoding the lamin B receptor (LBR). Methods: A familial case of three fetuses of a consanguineous Greek couple is presented including prenatal, physical, radiographic, histopathologic, and molecular genetic findings. Results: The tentative diagnosis of Greenberg skeletal dysplasia based on pathological findings was confirmed by the identification of a homozygous, N547D amino acid substitution in the LBR gene in the third affected fetus. Conclusion: The present case represents the ninth described case of Greenberg dysplasia and the second case of Greek origin. The characteristic 'moth-eaten' radiographic appearance is already seen at 13 weeks' gestational age. Copyright © 2008 John Wiley & Sons, Ltd

Use of uterine Doppler in an Australian level II maternity hospital

The definitive version is available at www.blackwell-synergy.comObjective: To evaluate the clinical usefulness of uterine Doppler. Design: Retrospective study between March 2001 and March 2003. Setting: A high-risk population of pregnant women in a busy level II Maternity unit. Methods: Resistance index (RI) measurements of the right and left uterine artery were obtained by using pulsed wave Colour Doppler. The presence of a unilateral or bilateral early diastolic notch was noted. An abnormal result was defined as a mean RI ≥ 0.58 with no, one or two notches or a mean RI < 0.58 in the presence of bilateral notches. Results: Pre-eclampsia was found in 45 (24.7%) women, gestational hypertension (GH) in 22 (12.1%) and intrauterine growth restriction (IUGR) in 42 (23.1%) of women included (total 59.9%). In the overall group, 127 (69.8%) women were found to have abnormal uterine artery Doppler results and 55 (30.2%) of patients had a normal Doppler study. No significant differences were found between the group of women with abnormal uterine artery Doppler and the women with a normal velocity waveform in the prediction of pre-eclampsia, IUGR and GH, this was also true in the various high-risk-subgroups. Conclusions: Uterine Doppler is not particularly useful to the obstetrician in the management of patients with an a priori very high risk to develop uteroplacentalMariëtte J. C. Nagtegaal, Suzanne Van Rijswijk, Steward McGavin, Gus Dekkerhttp://www.blackwell-synergy.com/doi/abs/10.1111/j.1479-828X.2005.00469.

Genetic skeletal disorders of the fetus and infant: Pathologic and molecular findings in a series of 41 cases

BACKGROUND: Genetic skeletal disorders of the fetus and infant are a large group of genetic disorders, comprising the groups formerly assigned as skeletal dysplasias (osteochondrodysplasias), dysostoses, and malformation syndromes with a skeletal component. Genetic skeletal disorders may be prenatally detected by ultrasonography or result in intrauterine or early postnatal death, constituting one difficult diagnostic field met by the pathologist who performs the perinatal autopsy. METHODS: In this retrospective study, we have gathered radiologic, physical, histopathologic, and molecular data regarding 41 cases of genetic skeletal disorders diagnosed among 1980 fetal and perinatal autopsies over a 10-year period. RESULTS: Our series of cases were classified according to the 2006 Nosology and Classification of Genetic Skeletal Disorders. The overall frequency of genetic skeletal disorders was 1:48 autopsies. The FGFR3 group and osteogenesis imperfecta type 2 were the more frequently encountered disorders. The mean gestational age at autopsy was 21.9 weeks (range, 12-37 weeks). A final diagnosis was obtained in 95% of cases. Genetic skeletal disorders were detected by prenatal ultrasound in 90% of cases, with a correct typing of the disorder achieved in only 34%. Molecular analysis was confirmative in 5 cases. CONCLUSIONS: The central role of the perinatal pathologist in collaboration with specialized services is essential for the correct interpretation of the radiologic, physical, and histopathologic findings, to accurately classify specific types of genetic skeletal disorders and enable genetic counseling. © 2009 Wiley-Liss, Inc