Baraitser-Winter cerebrofrontofacial syndrome

Baraitser-Winter Cerebrofrontofacial syndrome (BWCFF) [BRWS; MIM #243310, 614583] is a rare developmental disorder affecting multiple organ systems. It is characterised by intellectual disability (mild to severe) and distinctive facial appearance (metopic ridging/trigonocephaly, bilateral ptosis, hypertelorism). The additional presence of cortical malformations (pachygyria/lissencephaly) and ocular colobomata are also suggestive of this syndrome. Other features include moderate short stature, contractures, congenital cardiac disease and genitourinary malformations. BWCFF is caused by missense mutations in the cytoplasmic beta- and gamma-actin genes ACTB and ACTG1. We provide an overview of the clinical characteristics (including some novel findings in four recently diagnosed patients), diagnosis, management, mutation spectrum and genetic counselling

Baraitser-Winter cerebrofrontofacial syndrome: Delineation of the spectrum in 42 cases

Baraitser-Winter, Fryns-Aftimos and cerebrofrontofacial syndrome types 1 and 3 have recently been associated with heterozygous gain-of-function mutations in one of the two ubiquitous cytoplasmic actin-encoding genes ACTB and ACTG1 that encode β- and γ-actins. We present detailed phenotypic descriptions and neuroimaging on 36 patients analyzed by our group and six cases from the literature with a molecularly proven actinopathy (9 ACTG1 and 33 ACTB). The major clinical anomalies are striking dysmorphic facial features with hypertelorism, broad nose with large tip and prominent root, congenital non-myopathic ptosis, ridged metopic suture and arched eyebrows. Iris or retinal coloboma is present in many cases, as is sensorineural deafness. Cleft lip and palate, hallux duplex, congenital heart defects and renal tract anomalies are seen in some cases. Microcephaly may develop with time. Nearly all patients with ACTG1 mutations, and around 60% of those with ACTB mutations have some degree of pachygyria with anteroposterior severity gradient, rarely lissencephaly or neuronal heterotopia. Reduction of shoulder girdle muscle bulk and progressive joint stiffness is common. Early muscular involvement, occasionally with congenital arthrogryposis, may be present. Progressive, severe dystonia was seen in one family. Intellectual disability and epilepsy are variable in severity and largely correlate with CNS anomalies. One patient developed acute lymphocytic leukemia, and another a cutaneous lymphoma, indicating that actinopathies may be cancer-predisposing disorders. Considering the multifaceted role of actins in cell physiology, we hypothesize that some clinical manifestations may be partially mutation specific. Baraitser-Winter cerebrofrontofacial syndrome is our suggested designation for this clinical entity

Evaluation of effectiveness of quantitative fluorescent- Polymerase chain reaction (QF-PCR) technique Using D21S1411 short tandem repeat (STR) marker in the rapid prenatal diagnosis of down syndrome

Giriş ve Amaç: Doğum öncesi tanı için en sık endikasyon, fetusda artmış trizomi 21 riskidir. Bu çalışmada, trizomi 21’in hızlı doğum öncesi tanısında QF-PCR tekniğinin klinik uygulanabilirliğinin gösterilmesi amaçlandı. Ayrıca, bu teknikle trizomi tanısı koyabilmek için gerekli en az hücre sayısı ve bu değerin gebelik haftalarıyla ilişkisi değerlendirildi. Olgular ve Yöntem: 224 gebeye ait amniyon sıvısında hücre sayımı yapıldı ve gebelik haftalarına göre sınıflandırıldı. Amniyon sıvısında bulunan total ve canlı hücre sayısı ile canlı hücre oranının gebelik haftasıyla istatistiksel olarak anlamlı bir ilişkisi olduğu (p<0.001) gösterildi. 135 olgudan DNA ayrımı yapıldı. DNA örnekleri D21S1411 belirleyici ile QF-PCR kullanılarak çoğaltıldı. Bulgular: Normal örneklerin pik oranı ortalama 1.1 ve trizomik diallelik örneklerin pik oranları 2.0 olarak hesaplandı. 14–22. gebelik haftaları arasında 0.1–1.9 ml amniyon sıvısından elde edilen amniyosit sayısının QF-PCR ile tanı koymak için yeterli olduğu gösterilmiştir. QF-PCR testinin trizomi 21’i teşhis etmede duyarlılığının %90, seçiciliğinin %93.6, pozitif ve negatif öngörü değerlerinin ise %100 olduğu hesaplanmıştır. D21S1411 belirleyicinin heterozigozite oranının ise 0.8320 olduğu gösterilmiştir. Sonuç ve Tartışma: D21S1411 belirleyicinin Türk toplumunda trizomi 21 tanısı için güvenle kullanılabileceği sonucuna varılmıştır. QF-PCR analizi, trizomi 21’in hızlı tanısında uygulanabilecek yardımcı bir testtir. Daha fazla sayıda belirleyici ile çalışmak, testin duyarlılığını artıracaktır.Introduction: The most frequent indication for prenatal diagnosis is the increased risk of trisomy 21 in fetus. In this study, it is targeted to show the clinical practicability of QF-PCR technique in the rapid diagnosis of trisomy 21. Additionally, the minumum required number of cells in order to diagnose trisomy and the minumum number of amniocytes in relation to the gestational week were also evaluated with this technique. Material and Method: Amniotic fluid cell counts were carried out in 224 pregnant women and the findings were classified according to the gestational week. It was proved that there is a statistically significant (p&lt;0.001) relationship between the total and viable cell number, viable cell ratio in amniotic fluid and the gestational week. The DNA isolation was made for 135 case. The DNA samples were amplified with using the determinant of D21S1411 locus on chromosome 21 by QF-PCR. Results: It was calculated that the average peak ratio of normal samples is 1.1 and the peak ratio of trisomic diallelic samples is 2.0. It was shown that amniocyte number obtained from 0.1&amp;#8211;1.9 ml amniotic fluid of 14&amp;#8211;22 gestational weeks woman is sufficient to diagnose trisomy by QF-PCR within an acceptable range of certainty. It was calculated that the sensitivity of QF-PCR test in diagnosing trisomy 21 was 90%, specificity was 93.6%, positive and negative predictive values were 100%. It was indicated that the heterozygosity rate of D21S1411 marker was 0.8320. Conclusion: It is concluded that D21S1411 marker can safely be applied in Turkish population for diagnosis of trisomy 21. QF-PCR analysis is a helping test that could be used for rapid prenatal diagnosis of trisomy 21. Studying with more number of markers will increase the sensitivity of the PCR test

Hematopoietic stem cell transplantation in relapsed or refractory extracranial primitive neuroectodermal tumor of children and adolescents: A multicenter survey study

WOS: 000361247200483

Spatio-temporal variability of the size-fractionated primary production and chlorophyll in the Levantine Basin (northeastern Mediterranean)

Summary: Spatial and temporal variations in size-fractionated primary production (PP) and chl a, in relation to ambient physicochemical parameters, were studied in the three distinct ecosystems of northeastern Levantine Basin namely eutrophic Mersin Bay, mesotrophic Rhodes Gyre, and oligotrophic offshore waters. These ecosystems were visited in July and September 2012 and March and May 2013. Total primary production (TPP) rates ranged between 0.22 and 17.8 mg C m−3 h−1 within the euphotic zone, whereas depth-integrated TPP rates were in the range 21.5–348.8 mg C m−2 h−1 (mean: 105.5 ± 88 mg C m−2 h−1), with the lowest rates recorded for offshore waters. Similar spatio-temporal variations were observed in chl a concentrations, ranging from 2.3 to 117.9 mg m−2 (mean: 28.9 ± 24.9 mg m−2) in the study area. The Mersin Bay TPP rates have exceeded almost 8–12 times those measured in the offshore waters and the Rhodes Gyre; however, the chl a concentrations measured in coastal waters (0.343 mg m−3) and the Rhodes Gyre (0.308 mg m−3) were only threefold larger than the offshore values. PP and chl a were dominated by picoplankton in the study area whereas small nanoplankton, being the most active, displayed the highest assimilation ratio in offshore waters (6.8) and the Rhodes Gyre (2.8). In the upper-layer waters depleted of P (0.02–0.03 μM) of the northeastern Mediterranean, a positive correlation was observed between NO3 + NO2 and PP (and thus, chl a), which strongly suggests that reactive P and inorganic nitrogen are co-limiting factors in the production and biomass distribution of the phytoplankton community in both shelf and offshore waters. Keywords: Primary production, Chlorophyll, Picoplankton, Rhodes Gyre, Cilician Basin, Levantine Basi