Severe congenital microcephaly with AP4M1 mutation, a case report

Background: Autosomal recessive defects of either the B1, E1, M1 or S1 subunit of the Adaptor Protein complex-4 (AP4) are characterized by developmental delay, severe intellectual disability, spasticity, and occasionally mild to moderate microcephaly of essentially postnatal onset. Case presentation: We report on a patient with severe microcephaly of prenatal onset, and progressive spasticity, developmental delay, and severe intellectual deficiency. Exome sequencing showed a homozygous mutation in AP4M1, causing the replacement of an arginine by a stop codon at position 338 of the protein (p.Arg338X). The premature stop codon truncates the Mu homology domain of AP4M1, with predicted loss of function. Exome analysis also showed heterozygous variants in three genes, ATR, MCPH1 and BLM, which are known causes of autosomal recessive primary microcephaly. Conclusions: Our findings expand the AP4M1 phenotype to severe microcephaly of prenatal onset, and more generally suggest that the AP4 defect might share mechanisms of prenatal neuronal depletion with other genetic defects of brain development causing congenital, primary microcephaly

Spin asymmetry A_1^d and the spin-dependent structure function g_1^d of the deuteron at low values of x and Q^2

We present a precise measurement of the deuteron longitudinal spin asymmetry A_1^d and of the deuteron spin-dependent structure function g_1^d at Q^2 < 1 GeV^2 and 4*10^-5 < x < 2.5*10^-2 based on the data collected by the COMPASS experiment at CERN during the years 2002 and 2003. The statistical precision is tenfold better than that of the previous measurement in this region. The measured A_1^d and g_1^d are found to be consistent with zero in the whole range of x.Comment: 17 pages, 10 figure

THE PRESENT STATUS OF THE GERM-CELL PROBLEM IN VERTEBRATES

(i) Morphological studies relating to the origin and differentiation of the definitive germ cells in vertebrates have, as indicated, resulted in conflicting views. In many instances two or more competent investigators who have studied the same form have reached different conclusions. (2) Some contend that the germ cells are set aside from the soma during the early stages of embryonic development, and that these alone serve as the progenitors of the functional sex cells. (3) Others recognize an early differentiation of sex cells but hold that these are supplemented by others produced from the somatic epithelium of the gonad in late embryonic or post-embryonic stages. (4) Another group recognizes the early differentiated cells as germ cells but contend that these all degenerate and that the definitive ones are formed from the germinal epithelium. These degenerating germ cells are believed by certain authors to be a phylogenetic recapitulation of the condition in lower forms. (5) Finally, yet another group contends that the so-called primordial germ cells are not germ cells at all but are enlarged cells in some stage of mitosis or in some specific metabolic phase. This group believes that all germ cells are derived from the somatic cells of the germinal epithelium. (6) Experimental work supports the view that the primordial germ cells, which are recognized early, are the progenitors of the definitive sex cells. When these primordial germ cells are prevented from reaching the site of the developing gonad the individual fails to develop sex cells, although a sterile gonad and its associated structures may develop. (7) I suggest that the observed proliferation of germ cells from the germinal epithelium, reported by numerous investigators, can be interpreted in another way by a thorough study of the enlarged germ cells in relation to the epithelium. It seems probable that the cells of the epithelium, which form functional sex elements, are not and never were a part of the mesothelial covering, but are cells which were segregated early, and are merely stored in the epithelium.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74677/1/j.1469-185X.1945.tb00313.x.pd

Phenotypes and genotypes in non-consanguineous and consanguineous primary microcephaly: High incidence of epilepsy.

Primary microcephaly (PM) is defined as a significant reduction in occipitofrontal circumference (OFC) of prenatal onset. Clinical and genetic heterogeneity of PM represents a diagnostic challenge. We performed detailed phenotypic and genomic analyses in a large cohort (n = 169) of patients referred for PM and could establish a molecular diagnosis in 38 patients. Pathogenic variants in ASPM and WDR62 were the most frequent causes in non-consanguineous patients in our cohort. In consanguineous patients, microarray and targeted gene panel analyses reached a diagnostic yield of 67%, which contrasts with a much lower rate in non-consanguineous patients (9%). Our series includes 11 novel pathogenic variants and we identify novel candidate genes including IGF2BP3 and DNAH2. We confirm the progression of microcephaly over time in affected children. Epilepsy was an important associated feature in our PM cohort, affecting 34% of patients with a molecular confirmation of the PM diagnosis, with various degrees of severity and seizure types. Our findings will help to prioritize genomic investigations, accelerate molecular diagnoses, and improve the management of PM patients

Autosomal recessive primary microcephaly due to ASPM mutations: An update (vol 39, pg 319, 2018)

status: publishe

Optical monitoring of BL Lac object S5 0716+714 and FSRQ 3C 273 from 2000 to 2014

Using the 1.56m telescope at the Shanghai Observatory (ShAO), China, we monitored two sources, BL Lac object S5 0716+714 and Flat Spectrum Radio Quasar (FSRQ) 3C 273. For S5 0716+714, we report 4969 sets of CCD (Charge-coupled Device) photometrical optical observations (1369 for V band, 1861 for R band and 1739 for I band) in the monitoring time from Dec.4, 2000 to Apr.5, 2014. For 3C 273, we report 460 observations (138 for V band, 146 for R band and 176 for I band) in the monitoring time from Mar. 28, 2006 to Apr. 9, 2014. The observations provide us with a large amount of data to analyze the short-term and long-term optical variabilities. Based on the variable timescales, we can estimate the central black hole mass and the Doppler factor. An abundance of multi-band observations can help us to analyze the relations between the brightness and spectrum. We use Gaussian fitting to analyze the intra-day light curves and obtain the intra-day variability (IDV) timescales. We use the discrete correlation function (DCF) method and Jurkevich method to analyze the quasi-periodic variability. Based on the VRI observations, we use the linear fitting to analyze the relations between brightness and spectrum. The two sources both show IDV properties for S5 0716+714. The timescales are in the range from 17.3 minutes to 4.82 hours; for 3C273, the timescale is 35.6 minutes. Based on the periodic analysis methods, we find the periods P(V) = 24.24 days, P(R)=24.12 days, P(I)=24.82 days for S5 0716+714, and P = 12.99, 21.76 yr for 3C273. The two sources displayed the "bluer-when-brighter" spectral evolution properties. S5 0716+714 and 3C 273 are frequently studied objects. The violent optical variability and IDV may come from the jet. Gaussian fitting can be used to analyze IDVs. The relations between brightness (flux density) and spectrum are strongly influenced by the frequency.Comment: 28 pages, 3 table