Prawdopodobieństwo wystąpienia różnych patologii ciąży w rodzinach nosicieli translokacji chromosomowych wzajemnych angażujących chromosom 13

Summary Objectives: The aim of study was to estimate the probability rates for unfavorable pregnancy outcomes in carriers of reciprocal chromosomal translocations involving 13 chromosome (RCT-13q). Material and methods: We collected total empirical data about 232 pregnancies of 56 carriers coming from 28 pedigrees. RCT classification was based on classic cytogenetic methods for interpretation of breakpoint position. The probability rates of particular type of pathology related to the total number of pregnancies after ascertainment correction have been calculated with the help of Stengel-Rutkowski and Stene method. Results: The risk figures for unbalanced offspring after 2:2 disjunction and adjacent-1 segregation for the whole group of pedigrees were calculated as 5.2+/-1.7% (9/173) – medium risk, for maternal (MAT) and paternal (PAT) carriers were about 6.2+/-2.3% (7/173) and 4.8+/-3.3% (2/42) respectively. Considering different segment lengths of 13q, similar values for shorter and longer segments were obtained [4.3+/-1.9% (5/115) for 13q21→qter and 7.0+/-3.3% (4/58) for 13q12→qter]. The risk figures for miscarriages as 36.4+/-3.6% (63/173) and for stillbirths/early death as 4.6+/-31.6% (8/173) were obtained. The risk figures for unbalanced offspring after 3:1 disjunction were calculated as 7.7+/-7.45 (9/13). Conclusions: 1. Risk figures for different pregnancy outcomes are differ among particular forms of pathology 2. Probability rate for unbalanced progeny at birth was calculated as a medium risk and similar values for carriers of different segments of 13q were obtained 3. Probability rate for miscarriages was high but risk for stillbirths/early deaths of newborn was low 4. No differences in values of rate for particular forms of pathology were found for maternal and paternal carriers of RCT -13q.Streszczenie Cel pracy: Celem badań było oszacowanie prawdopodobieństwa wystąpienia różnych patologii ciąży w rodzinach nosicieli translokacji chromosomowych wzajemnych angażujących długie ramię chromosomu 13 (TCW-13q). Materiał i metody: Materiał do analizy stanowiły dane empiryczne i cytogenetyczne o 232 ciążach 56 nosicieli, uzyskane z 28 rodowodów nosicieli TCW ryzyka pojedynczego niezrównowaęenia segmentu angażujących chromosom 13. Prawdopodobieństwo wystąpienia różnych patologii ciąży oszacowano metodą Stengel-Rutkowski i Stene. Wyniki: Prawdopodobieństwo urodzenia dziecka z niezrównoważonym kariotypem w rodzinach nosicieli TCW z udziałem chromosomu 13 po segregacji 2:2 rozdziale przyległym typu 1 wynosiło 5,2+/-1,7% (9/173) – ryzyko średnie; po segregacji 3:1 ryzyko wynosiło 7,7+/-7,4% (9/13) – ryzyko średnie. W przypadku nosicielstwa matczynego (MAT) osiągnęło wartość 6,2+/-2,3% (7/173), zaś ojcowskiego (PAT) wartość 4,8+/-3,3% (2/42). Rozpatrując poszczególne segmenty chromosomu 13, prawdopodobieństwo miało następujące wartości: segment 13q21.2→qter - 4,3+/-1,9% (5/115), segment 13q12→qter – 7+/-3,3% (4/58). Ryzyko utraty ciąży na skutek ciąż obumarłych określono na 4,6+/-1,6% (8/173), natomiast ryzyko poronień samoistnych 36,4+/-3,6% (63/173). Wnioski: 1. Wielkości prawdopodobieństwa wystąpienia poszczególnych patologii ciąży w rodzinach nosicieli TCW-13q są różne. 2. Wielkość prawdopodobieństwa urodzenia dziecka z niezrównoważonym kariotypem należy do grupy ryzyka średniego; uzyskano podobne wartości w rodzinach nosicieli poszczególnych segmentów chromosomu 13. 3. Wielkość ryzyka genetycznego poronień samoistnych należy do grupy ryzyka wysokiego i jest wyższe w stosunku do ryzyka ciąż obumarłych przed terminem porodu (grupa ryzyka niskiego). 4. Nie stwierdzono różnic w wielkości wskaźników ryzyka dla poszczególnych form patologii ciąży w zależności od płci nosiciela

Ocena prawdopodobieństwa wystąpienia różnych patologii ciąży w rodzinach nosicieli translokacji chromosomowych wzajemnych angażujących chromosom 20

Carriership of reciprocal chromosome translocation (RCT) in a family may be the reason for malformation at birth, stillbirth, early neonatal death, and miscarriage due to unbalanced karyotype (monosomy/trisomy). The size of chromosome segments determined by the breakpoint position, kind of chromosome involved and the carrier’s gender may influence the probability rate for each category of the unfavorable pregnancy outcome in the family of the carrier of a particular RCT. Until now, the literature lacks reports on the risk values for particular forms of pregnancy outcomes in case of single segment imbalance, both the short (p) and the long arm (q) of chromosome 20. Objective: The aim of the study was to evaluate individual risk rates for unbalanced offspring at birth for single segment imbalance in the form of trisomy/monosomy and a separate evaluation risk figures for different pregnancy outcomes, depending on the size of the involved chromosome segment, its origin and carrier gender in families of RCT carriers involving chromosome 20 (RCT-20). In addition, practical application of the obtained results in the family with unique RCT t(13;20)(q14.1;p11.21) carriership has been shown. Material and methods: Total empirical data of 50 families (219 pregnancies) were collected from 19 pedigrees of RCT-20 carriers coming from different collections of RCT and available references. Cytogenetic studies were performed by GTG technique. The probability rates of particular type of pathology related to the total number of pregnancies after ascertainment correction have been done by segregation analysis according to the method of Stengel-Rutkowski and Stene. Results: The probability rate for unbalanced offspring at birth for carriers of RCT-20p was calculated as 5.5±1.8% (9/164) (medium risk). Considering parental gender of the carrier for maternal (MAT) and paternal (PAT) carriers, the probability rate values were similar i.e. 4.8±2.3% (4/84) and 4.9±2.8% (3/61), respectively. The risk figures for stillbirth/ early neonatal deaths were found as 0.6±0.6% (1/164) (low risk), but separately for MAT and PAT carriers they were: 1.2±1.2% (1/84) andNosicielstwo translokacji chromosomowej wzajemnej (TCW) w rodzinie może prowadzić do urodzenia potomstwa z wadami rozwojowymi, bądź być przyczyną wystąpienia różnych form patologii ciąży wywołanych niezrównoważonym kariotypem (monosomią/trisomią). Wielkość segmentów wyznaczonych przez położenie punktu złamania i rodzaj zaangażowanego chromosomu oraz płeć nosiciela wpływają na wielkość prawdopodobieństwa wystąpienia każdej z form patologii ciąży w rodzinie nosiciela danej TCW. Jak dotąd nie jest znana wielkość tych wskaźników w przypadku niezrównoważenia pojedynczego segmentu chromosomowego zarówno dla krótkiego (p) jak i długiego (q) ramienia chromosomu 20. Cel pracy: Celem badań było opracowanie indywidualnych wskaźników prawdopodobieństwa urodzenia dziecka z niezrównoważonym kariotypem na skutek monosomii/trisomii pojedynczego segmentu chromosomowego oraz wskaźników ryzyka wystąpienia poszczególnych patologii ciąży w zależności od wielkości segmentu i jego pochodzenia oraz płci nosiciela w rodzinach nosicieli TCW angażujących chromosom 20 (TCW-20). Zastosowanie uzyskanych wyników do opracowania porady genetycznej w rodzinie z nosicielstwem unikatowej translokacji t(13;20) (q14.1; p11.21) jako przykład ich praktycznego wykorzystania. Materiał i metody: Dane empiryczne i cytogenetyczne o 219 ciążach 50 nosicieli uzyskano z 19 rodowodów. Wielkość wskaźników opracowano metodą Stengel-Rutkowski z korektą oszacowania wg Stene. Wyniki: Prawdopodobieństwo urodzenia dziecka z niezrównoważonym kariotypem w rodzinach nosicieli TCW -20p wynosi: 5,5±1,8% (9/164), w tym w przypadku nosicielstwa matczynego 4,8±2,3% (4/84), a ojcowskiego 4,9±2,8% (3/61), natomiast w rodzinach nosicieli TCW-20q ok. 2,6% (0/20). Ryzyko wystąpienia ciąży obumarłej/wczesnego zgonu noworodka w rodzinach nosicieli TCW-20p szacuje się na 0,6±0,6% (1/164), natomiast nosicieli TCW-20q na ok. 2,6% (0/20). Ryzyko wystąpienia poronień samoistnych wynosi odpowiednio: 28,6±3,5% (47/164) i 50±11,2% (10/20). Wnioski: 1. Wskaźniki prawdopodobieństwa urodzenia dziecka z niezrównoważonym kariotypem, jak też wskaźniki ryzyka wystąpienia badanych form patologii ciąży wykazują różnice w zależności od pochodzenia i wielkości segmentu chromosomu 20. 2. Nie stwierdzono różnic w wielkości poszczególnych wskaźników w zależności od płci nosiciela

Preventive Role of L-Carnitine and Balanced Diet in Alzheimer’s Disease

The prevention or alleviation of neurodegenerative diseases, including Alzheimer’s disease (AD), is a challenge for contemporary health services. The aim of this study was to review the literature on the prevention or alleviation of AD by introducing an appropriate carnitine-rich diet, dietary carnitine supplements and the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) diet, which contains elements of the Mediterranean diet and the Dietary Approaches to Stop Hypertension (DASH) diet. L-carnitine (LC) plays a crucial role in the energetic metabolism of the cell. A properly balanced diet contains a substantial amount of LC as well as essential amino acids and microelements taking part in endogenous carnitine synthesis. In healthy people, carnitine biosynthesis is sufficient to prevent the symptoms of carnitine deficiency. In persons with dysfunction of mitochondria, e.g., with AD connected with extensive degeneration of the brain structures, there are often serious disturbances in the functioning of the whole organism. The Mediterranean diet is characterized by a high consumption of fruits and vegetables, cereals, nuts, olive oil, and seeds as the major source of fats, moderate consumption of fish and poultry, low to moderate consumption of dairy products and alcohol, and low intake of red and processed meat. The introduction of foodstuffs rich in carnitine and the MIND diet or carnitine supplementation of the AD patients may improve their functioning in everyday life

Limited survivability of unbalanced progeny of carriers of a unique t(4;19)(p15.32;p13.3): a study in multiple generations

Abstract Background Carriership of a reciprocal chromosomal translocation (RCT) involving the short arm of chromosome 4 (4p) may result in birth of a child with Wolf-Hirschhorn syndrome (WHS) due to monosomy 4p, a priori modified by the impact of the partner chromosome imbalance. Familial transmission studies of RCT enable obtaining empirical risk figures that are essential for genetic counseling. In this study, pedigree data from carriers of a unique t(4;19)(p15.32;p13.3), ascertained by two children with WHS phenotype, were collected through five generations and empirical risk for different pregnancy outcomes was assessed. In addition, the phenotype-karyotype correlation was studied in two unbalanced children against the phenotypes of children (literature data) with pure monosomy 4p15.32 → pter and pure trisomy 19p13.3 → pter, accordingly. The phenotype analysis was conducted using the catalogue of traits according to the Munich Dysmorphology Database. Pedigree segregation analysis was conducted by the direct method according to Stengel- Rutkowski et al. Results A double segment imbalance, trisomy 19p13.3 → pter with monosomy 4p15.32 → pter, was diagnosed in WHS progeny at birth. No essential modification of WHS phenotype by the additional trisomy 19p was observed, except for a limited survivability (death in infancy). Pedigree segregation analysis covered 39 relatives showed the probability rate for liveborn with unbalanced karyotype of 3.7 ± 3.6% (1/27), for stillbirth/neonatal death at 7.4 ± 5.0% (2/27), for miscarriage at 22.2 ± 8.0% (6/27), for the chance of having a baby without unbalanced karyotype was estimated at 66.7 ± 9.1% (18/27). In addition, the value of 7.4% for genetic counseling for any carrier of RCT at risk for single segment 19p13.3 → pter imbalance at birth was evaluated as such value have not been estimated so far. Conclusion Carriership of a t(4;19)(p15.32;p13.3) is at low risk for an unbalanced child at birth and for stillbirth/neonatal death but high for miscarriages. The chance of having a baby without unbalanced karyotype was estimated to be high. Monosomy 4p15.32 → pter together with trisomy 19p13.3 → pter as a double segment imbalance in children with WHS may be connected with a limited survivability in infancy

Additional file 1: Table S1. of Limited survivability of unbalanced progeny of carriers of a unique t(4;19)(p15.32;p13.3): a study in multiple generations

Phenotype characteristics of two children with monosomy of 4p15.32→pter together with trisomy 19p13.3→pter compared with three children with the pure monosomy 4p15.32 →pter (Iwanowski et al. [2]) and two children with the pure trisomy 19p13.3→pter (Andries et al. [7], Ishikawa et al. [8]). (DOC 177 kb

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.The article is available via Open Access. Click on the 'Additional link' above to access the full-text.Published version, accepted version (12 month embargo