QF-PCR and MLPA: a reliable molecular system to detect chromosomal alterations in miscarriages.

PURPOSE OF INVESTIGATION: The aim of this study was to assess the efficacy of the quantitative fluorescent-polymerase chain reaction (QF-PCR) and multiplex ligation-dependent probe amplification (MLPA) combined system to detect chromosome alterations in miscarriage products, as an alternative to conventional cytogenetic testing. MATERIAL AND METHODS: This study was conducted between 2011 and 2015 on 264 samples, analyzed using the combined system: QF-PCR/MLPA. This approach first analyzed miscarriage products for chromosomes 13, 18, 21, X and Y, using QF-PCR analysis; in case of ovular fragments, an analysis of maternal DNA was carried out in order to establish the origin of material. Whenever fetal origin was determined, MLPA analysis on the subtelomeric regions was car- ried out. RESULTS: On 264 miscarriages analyzed, 229 were of fetal origin and produced the following results: 53.7% normal and 46.3% pathological. Of the latter, 74.4% were autosomal aneuploidies, 10.4% triploidies, 8.5% sex chromosomal aneuploidies, 3.7% structural alterations, and 2.7% multiple aneuploidies. Results from QF-PCR were obtained from all samples, whereas unambiguous MLPA re- sults were obtained in about 90% of all cases. CONCLUSION: This approach results being highly effective for examining all chromosome aneuploidies, triploidies, as well as structural unbalanced alterations in the subtelomeric regions.

MYOCLONIC ASTATIC EPILEPSY IN A PATIENT WITH A DE NOVO 4q21.22q21.23 MICRODUPLICATION.

Myoclonicastatic epilepsy (MAE) is a rare form of symptomatic generalized epilepsy of uncertain etiology. To search the possible genetic basis of the disorder, here we investigate a 15 year-old patient with MAE, who is the only person presenting epilepsy in the family. High resolution array-CGH analysis was conducted on DNA extracted from peripheral blood of the patient and the parents. The copy number variant(s) (CNVs) identified were further confirmed by Fluorescent In Situ Hybridization (FISH). The array-CGH identified a de novo microduplication of about 778 Kb in the chromosome region 4q21.22-q21.23, involving 11 genes. This is the first report of a de novo CNV in MAE. The genes involved in the duplication are potential candidates that can be investigated in the future to determine their exact role in the etiopathogenesis of the disorder. However, we suggest performing microarray chromosomal analysis in patients with MAE, since rare de novo CNVs could be identified, and this is known to affect the diagnostic process and recurrence risk assessment.

Prognostic value of 24-hour blood pressure in pregnancy.

CONTEXT: Elevated blood pressure (BP) measured at the physician's office may reflect true hypertension or white coat hypertension (WCH). The prognostic value of WCH among pregnant women is unknown. OBJECTIVE: To assess the prognostic value of WCH in pregnancy. DESIGN: Prospective cohort study conducted between September 1994 and October 1997. SETTING: Community hospital. PATIENTS: Women without preexisting hypertension and not treated with antihypertensive drugs aid with high (n = 148) or normal (n = 106) office BP (high office BP was defined as > or =140 mm Hg systolic and/or > or =90 mm Hg diastolic) matched for gestational age during their third trimester of pregnancy. All women underwent 24-hour noninvasive BP monitoring, and women without hypertension on 24-hour monitoring (125/74 mm Hg or less for average 24-hour BP) with office hypertension were classified as having WCH. Women were followed up through the end of pregnancy. MAIN OUTCOME MEASURES: Duration of pregnancy, gestational hypertension, preeclampsia or eclampsia, cesarean delivery, placental and neonatal weight, and length of maternal and neonatal hospital stays for those with and without elevated office BP. RESULTS: After application of exclusion criteria, data for 7 women were removed from the analysis. For the remaining subjects, in the group with elevated BP, prevalence of WCH was 29.2% (42/144). Duration of pregnancy was similar in the normotensive and WCH groups (39.6 vs 39.8 weeks; P = .50), but shorter (38.3 weeks; P<.001) in the true hypertension group. Incidence of preeclampsia was similar in the normotensive and WCH groups (5.8% vs 7.1 %; P = .86) but higher in the true hypertension group (61.7%; P<.001). Frequency of cesarean delivery was lower in the normotensive (12.4%) than in the WCH (45.2%; P = .008) and true hypertension (41.1 %; P = .009) groups. Neonatal weight was lower (P<.001) in the true hypertension (mean, 2911 g) than in the normotensive (3336 g) and WCH groups (3435 g), which did not differ (P = .68). The duration of neonatal hospital stay did not differ between the normotensive and the WCH group (5.3 vs 6.9 days; P = .13) but was longer in the true hypertension group (12.3 days; P<.001). CONCLUSIONS: In women with elevated BP during their third trimester of pregnancy, 24-hour BP was superior to office BP (distinguishing true hypertension from WCH) for prediction of the outcome of pregnancy. Outcomes in the normotensive and WCH group were comparable, but the increased incidence of cesarean delivery in the WCH group may reflect decision-making processes influenced by office BP.

Twenty four-hour ambulatory blood pressure monitoring in women with pre-eclampsia.

The aim of our study was to evaluate by means of ambulatory 24 h monitoring the diurnal systolic (SBP) and diastolic (DBP) blood pressure profiles in a group (n = 18) of gravid patients with pre-eclampsia compared with a group (n = 17) of healthy control subjects matched for age and week of gestation to assess whether: (i) ambulatory BP is also raised in pre-eclampsia; (ii) the increase of BP, if present, occurs to the same extent during both daytime and night; and (iii) a blunted BP pattern is consistently present in pre-eclampsia. BP was recorded at intervals of 15 min for 25 h using a TM2420 non-invasive pressurometer. The presence of a circadian rhythm of BP was assessed by cosinor analysis. SBP was higher in women with pre-eclampsia (24 h average 115 +/- 11 vs. 136 +/- 12, P = 6 x 10(-6); daytime 117 +/- 12 vs. 139 +/- 13, P = 6 x 10(-6); night 110 +/- 11 vs. 129 +/- 14, P = 5 x 10(-5) as well as DBP (24 h average 67 +/- 5 vs. 86 +/- 6, P = 8 x 10(-12); daytime 69 +/- 6 vs. 89 +/- 5, P = 2 x 10(-11); night 62 +/- 4 vs. 80 +/- 8, P = 5 x 10(-10).(ABSTRACT TRUNCATED AT 250 WORDS)

[Spondylo-costal dysostosis: presentation of a new case with autosomal dominant heredity and discussion of problems in genetic counseling]. / Disostosi spondilo-costale: presentazione di un nuovo caso ad ereditarietà autosomica dominante e discussione delle problematiche della consulenza genetica.

The Authors report a new family with spondylo-costal dysplasia in which three members in three generation are affected. The genetic heterogeneity of the condition and its implication in genetic counseling is discussed.