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

Promene mineralnih sastava mandibulnog tela u osteoporozi

The aim of investigation was to determine physical-chemic characteristics of selected segments of mandibular corpuses from 2 cadavers which would be indicators to determine changes of bone compositions due to osteoporosis. 3 samples from massive mandibular body from cadaver where teeth of lower arch persisted and 3 samples from mandibular edentulous corpus from another cadaver were investigated. External borders of samples were assigned. In the same x-ray exposing and in identical processing 2 orthopantomographs were made and optical densities(OPDs) of regions of interest were analyzed using DT II 05 (EU(England,UK)). Samples of similar dimensions were cut and then analyzed by scanning-electronic microscopy (Philips,EU). Using bensol as liquid phase on 200C in pycnometer, densities of samples of bones were analyzed. Values of OPDs, in U/mm2, amount: -2.48-sample(S)l, -2.86 S2, -2.51 S3, -0.90 S4, -1.40 S5, -0.62 S6. Statistically significant, to p lt 0.01 totals of cancellous sites were established in comparisons: of S6 and of S4, of SI and of S5 as well as of S2 and of S4, and to p lt 0.1 were established in comparisons: of Sl and of S3, of SI and of S6, of S2 and of S5, of S2 and of S6, of S3 and of S4, as well as of S6 and of S4. Mean thickness of cortical lamellae, in mm, amount: 17.9 ± 7.51 in S1, 12.22 + 1.17 in S2, 31.03 ± 8.91 in S3, 9.31 ± 3.89 in S4, 23.9 ± 11.7 in S5 and 4.06 ± 1,02 in S6. Densities in g/cm3, amount: 1.9658 for S1, 2.1141 for S2, 2.0748 for S3, 2.1296 for S4 2.2231 for S5 and 2.1357 for S6. Differences of densities and of compositions of non-osteoporotic mandibular-body samples, and of mandibular osteoporotic samples were determined.Osteoporoza jeste značajno i zastupljeno oboljenje kada dominiraju procesi razgrađivanja kostnih supstanci u humanim organizmima. Za razliku od činjenica da u literaturi postoje brojni prikazi – makroskopski patološki preparati, mikroskopski patološki preparati, šematizovane ilustracije itd. skoro da nema podataka ni o promenama fizičkih parametara, niti o uticajima kompleksnih hemijskih jedinjenja u kostnim supstancama izmenjenim usled osteoporoza na fizičko-hemijske osobenosti izmenjene kosti, tako da dosta toga još uvek nije ispitano u vezi karakteristika, izmena sastava i fizičko-hemijske osobenosti osteoporoznih kosti. (Kanis 1994; 1996, WHO 1994 Kršljak 1995, Novaković i Giordani 1996, Poštić, Marković, Veselinović Tijanić i Zec 2001). Svakako bi trebalo da bude interesantno i značajno proceniti šta je izmenjeno u makrostrukturama i šta je sve izmenjeno u mikrostrukturama kosti oštećenih usled osteoporoza. Čini se da je važno utvrditi kako bi trebalo delovati na nivou jedinjenja i potencijalno na nivou molekula. Stoga je potrebno ispitati kako bi, na osnovu izmena u mikrostrukturama kosti, trebalo inicirati pozitivno remodelovanje kostne supstance, da li su formirana jedinjenja kakva je potrebno razgraditi zato što su apsolutno nepovoljna ili je moguće delovati, bez obzira na formirana odnosno preformirana jedinjenja, apozicijama potrebnih i u smislu osteogenih potencijala kvalitetnih jedinjenja na nivoima mikrostruktura. Ispitivanjima fizičko-hemijskih promena mikrostruktura kosti trebalo bi da budu utvrđeni karakteristični podaci, tako da bi na osnovu karakterističnih podataka trebalo proceniti da li bi aplikovanjima posebno sintetisanih jedinjenja odnosno specifičnih supstanci i aplikovanjima posebno kombinovanih supstanci bilo moguće poboljšati strukture kosti, ojačati segmente kosti - poboljšati fizičko-hemijska svojstva i sprečiti frakture segmenata kosti

Promene mineralnih sastava mandibulnog tela u osteoporozi

The aim of investigation was to determine physical-chemic characteristics of selected segments of mandibular corpuses from 2 cadavers which would be indicators to determine changes of bone compositions due to osteoporosis. 3 samples from massive mandibular body from cadaver where teeth of lower arch persisted and 3 samples from mandibular edentulous corpus from another cadaver were investigated. External borders of samples were assigned. In the same x-ray exposing and in identical processing 2 orthopantomographs were made and optical densities(OPDs) of regions of interest were analyzed using DT II 05 (EU(England,UK)). Samples of similar dimensions were cut and then analyzed by scanning-electronic microscopy (Philips,EU). Using bensol as liquid phase on 200C in pycnometer, densities of samples of bones were analyzed. Values of OPDs, in U/mm2, amount: -2.48-sample(S)l, -2.86 S2, -2.51 S3, -0.90 S4, -1.40 S5, -0.62 S6. Statistically significant, to p lt 0.01 totals of cancellous sites were established in comparisons: of S6 and of S4, of SI and of S5 as well as of S2 and of S4, and to p lt 0.1 were established in comparisons: of Sl and of S3, of SI and of S6, of S2 and of S5, of S2 and of S6, of S3 and of S4, as well as of S6 and of S4. Mean thickness of cortical lamellae, in mm, amount: 17.9 ± 7.51 in S1, 12.22 + 1.17 in S2, 31.03 ± 8.91 in S3, 9.31 ± 3.89 in S4, 23.9 ± 11.7 in S5 and 4.06 ± 1,02 in S6. Densities in g/cm3, amount: 1.9658 for S1, 2.1141 for S2, 2.0748 for S3, 2.1296 for S4 2.2231 for S5 and 2.1357 for S6. Differences of densities and of compositions of non-osteoporotic mandibular-body samples, and of mandibular osteoporotic samples were determined.Osteoporoza jeste značajno i zastupljeno oboljenje kada dominiraju procesi razgrađivanja kostnih supstanci u humanim organizmima. Za razliku od činjenica da u literaturi postoje brojni prikazi – makroskopski patološki preparati, mikroskopski patološki preparati, šematizovane ilustracije itd. skoro da nema podataka ni o promenama fizičkih parametara, niti o uticajima kompleksnih hemijskih jedinjenja u kostnim supstancama izmenjenim usled osteoporoza na fizičko-hemijske osobenosti izmenjene kosti, tako da dosta toga još uvek nije ispitano u vezi karakteristika, izmena sastava i fizičko-hemijske osobenosti osteoporoznih kosti. (Kanis 1994; 1996, WHO 1994 Kršljak 1995, Novaković i Giordani 1996, Poštić, Marković, Veselinović Tijanić i Zec 2001). Svakako bi trebalo da bude interesantno i značajno proceniti šta je izmenjeno u makrostrukturama i šta je sve izmenjeno u mikrostrukturama kosti oštećenih usled osteoporoza. Čini se da je važno utvrditi kako bi trebalo delovati na nivou jedinjenja i potencijalno na nivou molekula. Stoga je potrebno ispitati kako bi, na osnovu izmena u mikrostrukturama kosti, trebalo inicirati pozitivno remodelovanje kostne supstance, da li su formirana jedinjenja kakva je potrebno razgraditi zato što su apsolutno nepovoljna ili je moguće delovati, bez obzira na formirana odnosno preformirana jedinjenja, apozicijama potrebnih i u smislu osteogenih potencijala kvalitetnih jedinjenja na nivoima mikrostruktura. Ispitivanjima fizičko-hemijskih promena mikrostruktura kosti trebalo bi da budu utvrđeni karakteristični podaci, tako da bi na osnovu karakterističnih podataka trebalo proceniti da li bi aplikovanjima posebno sintetisanih jedinjenja odnosno specifičnih supstanci i aplikovanjima posebno kombinovanih supstanci bilo moguće poboljšati strukture kosti, ojačati segmente kosti - poboljšati fizičko-hemijska svojstva i sprečiti frakture segmenata kosti