Phenotypic expansion of the BPTF-related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL), defined primarily by developmental delay/intellectual disability, speech delay, postnatal microcephaly, and dysmorphic features, is a syndrome resulting from heterozygous variants in the dosage-sensitive bromodomain PHD finger chromatin remodeler transcription factor BPTF gene. To date, only 11 individuals with NEDDFL due to de novo BPTF variants have been described. To expand the NEDDFL phenotypic spectrum, we describe the clinical features in 25 novel individuals with 20 distinct, clinically relevant variants in BPTF, including four individuals with inherited changes in BPTF. In addition to the previously described features, individuals in this cohort exhibited mild brain abnormalities, seizures, scoliosis, and a variety of ophthalmologic complications. These results further support the broad and multi-faceted complications due to haploinsufficiency of BPTF.Genetics of disease, diagnosis and treatmen

Hit-Time and Hit-Position Reconstruction in Strips of Plastic Scintillators Using Multithreshold Readouts

In this article, a new method for the reconstruction of hit-position and hit-time of photons in long scintillator detectors is investigated. This research is motivated by the recent development of the positron emission tomography scanners based on plastic scintillators. The proposed method constitutes a new way of signal processing in Multi-Voltage-Technique. It is based on the determination of the degree of similarity between the registered signals and the synchronized model signals stored in a library. The library was established for a set of well defined hit-positions along the length of the scintillator. The Mahalanobis distance was used as a measure of similarity between the two compared signals. The method was validated on the experimental data measured using two-strips J-PET prototype with dimensions of 5x9x300 mm$^3$. The obtained Time-of-Flight (TOF) and spatial resolutions amount to 325~ps (FWHM) and 25~mm (FWHM), respectively. The TOF resolution was also compared to the results of an analogous study done using Linear Fitting method. The best TOF resolution was obtained with this method at four pre-defined threshold levels which was comparable to the resolution achieved from the Mahalanobis distance at two pre-defined threshold levels. Although the algorithm of Linear Fitting method is much simpler to apply than the Mahalanobis method, the application of the Mahalanobis distance requires a lower number of applied threshold levels and, hence, decreases the costs of electronics used in PET scanner