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.

Two unrelated families with variable expression of Fraser syndrome due to the same pathogenic variant in the FRAS1 gene.

We report on two unrelated families of Polish origin with variable expression of Fraser syndrome (FS; MIM#219000) due to homozygosity for the same pathogenic variant, c.6963_6964dup, of FRAS1. In one family, the disorder presented with perinatal and prenatal lethality. One affected female from family 2 who was followed-up for 32 years, represented a relatively favorable long-term outcome. She displayed the typical craniofacial dysmorphism, including right cryptophthalmos, cutaneous syndactyly, abnormalities of the stomathognatic system, bilateral atresia of the external ear canals resulting in conductive hearing loss, and malformations of the larynx, spleen, kidney, and genitourinary tract. Her intellectual capacities were normal. Our observations illustrate that expression and severity of FS, even when caused by the same pathogenic variant, may be quite different ranging from a lethal disorder to a condition with multiple physical malformations but normal psychomotor development. In addition, we propose that the FRAS1 c.6963_6964dup variant may be a founder mutation in the Polish population. Therefore, it would be reasonable to test specifically for this variant first in any FS1 patient of Polish ancestry.

A 23-year follow-up of a male with Hajdu-Cheney syndrome due to NOTCH2 mutation.

We present a natural history of a 32-year-old man with Hajdu-Cheney syndrome (HJCYS), because of the de novo truncating mutation in the exon 34 of NOTCH2 (c.6424-6427delTCTG, p.Ser2142ArgfsX4), who has been followed up for a period of 23 years (between 9 and 32 years). During follow-up, we observed abnormalities of vision, hearing, voice, and progression of craniofacial features in the form of skeletal dysplasia with affected skull, dentition, spine, limbs, fingers, and toes. Low bone mineral density and history of fragility fractures also suggested primary osteoporosis being a clinical manifestation. According to Stengel-Rutkowski, Schimanek, and Wernheimer (1984; Human Genetics, 6, 272-295), systematic data acquisition has been used for quantitative analysis of anthropological, radiographic, and clinical features at childhood, adolescence, and young adulthood separately. A detailed phenotype description together with the results of reanalysis of 14 reports so far published on patients with HJCYS and NOTCH2 mutation showed similar phenotype evolution with age. The spectrum of observed features may improve diagnostic tools for HJCYS at different periods of the lifespan.

ALG1-CDG: Clinical and Molecular Characterization of 39 Unreported Patients.

Congenital disorders of glycosylation (CDG) arise from pathogenic mutations in over 100 genes leading to impaired protein or lipid glycosylation. ALG1 encodes a ß1,4 mannosyltransferase that catalyzes the addition of the first of nine mannose moieties to form a dolichol-lipid linked oligosaccharide intermediate required for proper N-linked glycosylation. ALG1 mutations cause a rare autosomal recessive disorder termed ALG1-CDG. To date 13 mutations in 18 patients from 14 families have been described with varying degrees of clinical severity. We identified and characterized 39 previously unreported cases of ALG1-CDG from 32 families and add 26 new mutations. Pathogenicity of each mutation was confirmed based on its inability to rescue impaired growth or hypoglycosylation of a standard biomarker in an alg1-deficient yeast strain. Using this approach we could not establish a rank order comparison of biomarker glycosylation and patient phenotype, but we identified mutations with a lethal outcome in the first two years of life. The recently identified protein-linked xeno-tetrasaccharide biomarker, NeuAc-Gal-GlcNAc2 , was seen in all 27 patients tested. Our study triples the number of known patients and expands the molecular and clinical correlates of this disorder.

Meiotic and pedigree segregation analyses in carriers of t(4;8)(p16;p23.1) differing in localization of breakpoint positions at 4p subband 4p16.3 and 4p16.1.

PURPOSE: The purpose of this study was to compare meiotic segregation in sperm cells from two carriers with t(4;8)(p16;p23.1) reciprocal chromosome translocations (RCTs), differing in localization of the breakpoint positions at the 4p subband-namely, 4p16.3 (carrier 1) and 4p16.1 (carrier 2)-and to compare data of the pedigree analyses performed by direct method. METHODS: Three-color fluorescent in situ hybridization (FISH) on sperm cells and FISH mapping for the evaluation of the breakpoint positions, data from pedigrees, and direct segregation analysis of the pedigrees were performed. RESULTS: Similar proportions of normal/balanced and unbalanced sperm cells were found in both carriers. The most common was an alternate type of segregation (about 52 % and about 48 %, respectively). Unbalanced adjacent I and adjacent II karyotypes were found in similar proportions about 15 %. The direct segregation analysis (following Stengel-Rutkowski) of the pedigree of carriers of t(4;8)(p16.1;p23.1) was performed and results were compared with the data of the pedigree segregation analysis obtained earlier through the indirect method. The probability of live-born progeny with unbalanced karyotype for carriers of t(4;8)(p16.1;p23.1) was moderately high at 18.8 %-comparable to the value obtained using the indirect method for the same carriership, which was 12 %. This was, however, markedly lower than the value of 41.2 % obtained through the pedigree segregation indirect analysis estimated for carriers of t(4;8)(p16.3;p23.1), perhaps due to the unique composition of genes present within the 4p16.1-4p 16.3 region. CONCLUSIONS: Revealed differences in pedigree segregation analysis did not correspond to the very similar profile of meiotic segregation patterns presented by carrier 1 and carrier 2. Most probably, such discordances may be due to differences in embryo survival rates arising from different genetic backgrounds.

Co-segregation of Freiberg's infraction with a familial translocation t(5;7)(p13.3;p22.2) ascertained by a child with cri du chat syndrome and brachydactyly type A1B.

The identification of chromosomal breakpoints in association with human abnormal phenotypes can enable elucidation of gene function. We report on epiphyseal aseptic necrosis of the lesser head of the second metatarsal bone, known as Freiberg's infraction (FI), in two female carriers of the apparently balanced t(5;7)(p13.3;p22.2) ascertained by a 16-year-old girl with cri-du-chat syndrome and unusual skeletal features in association with an unbalanced translocation der(5) t(5;7)(p13.3;p22.2). Mapping of the chromosome breakpoints using fluorescent in situ hybridization (FISH) narrowed them to the coding sequence of ADAMTS12 on chromosome 5p13.3 and SDK1 on 7p22.2. In addition, several skeletal abnormalities classified as brachydactyly type A1B (BDA1B) were present in the proband and in both carriers of t(5;7)(p13.3;p22.2), suggesting a potential role of ADAMTS12 in the development of the BDA1B observed in this family.

[Systemic sclerosis. Part 2. Epigenetic factors in the pathogenesis of clinical manifestations]. / Twardzina ukladowa. Czesc 2. Czynniki epigenetyczne w patogenezie objawów klinicznych.

Systemic sclerosis is a complex autoimmune disease characterized by immune activation, fibrosis of the skin and internal organs and vasculopathy affecting predominantly the microvessels with a predilection for women. The genetic background of systemic sclerosis is still full of unanswered questions, with classical genetics able to explain only some systemic sclerosis cases. Novel advances concerning epigenetics give us new insight into pathogenesis of systemic sclerosis. This review focuses on results of recent reports on epigenetic modifications of the gene functions and X inactivation changes in pathogenesis of systemic sclerosis. Current evidence demonstrates DNA heavy methylation (FLI1, NOS3, BMPRII) and hypomethylation of regulatory genes (CD40L, CD70), histone code modifications, abnormal expression of large spectrum of microRNAs.

[Risk estimation of different pregnancy outcomes in the families of carriers of reciprocal chromosomal translocations involving chromosome 20]. / Ocena prawdopodobienstwa wystapienia róznych patologii ciazy w rodzinach nosicieli translokacji chromosomowych wzajemnych angazujacych chromosom 20.

UNLABELLED: 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 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) and < 0.8% (-/61), respectively. Risk figures for miscarriages were estimated as 28.6 +/- 3.5% (47/164) (high risk), with 32.1 +/- 5.1% (27/84) for maternal carriers and 32.7 +/- 6% (20/61) for paternal carriers. The risk figures for unbalanced offspring at birth for carriers of RCT-20q were calculated as about 2.6% (0/20) (low risk), for stillbirth/early neonatal death about 2.6% (-/20) (low risk) and for miscarriage 50 +/- 11.2% (10/20) (high risk). CONCLUSIONS: 1. The probability rates for unbalanced offspring at birth and for different categories of unfavorable outcomes show differences depending on the origin and the size of chromosome 20 segment. 2. There are no differences in the value of risk figures for particular form of pregnancy pathology in relation to carrier's gender.

[Probability rate of unbalanced offspring at birth and risk of unfavorable pregnancy outcomes in families of carriers of chromosomal reciprocal translocations involving chromosome 7]. / Ocena prawdopodobienstwa urodzenia dziecka z niezrównowafonym kariotypem oraz ryzyka wystqpienia róznych patologii ciazy w rodzinach nosicieli translokacji chromosomowych wzajemnych angazujacych chromosom 7.

INTRODUCTION: Carriership of reciprocal chromosomal translocation (RCT) may be the reason the occurrence of congenital malformations in the offspring, early neonatal death, stillbirth, and recurrent miscarriages due to unbalanced karyotype of gametes. The probability rate for individual categories of unfavorable outcomes depends on the kind of chromosome involved and is individually variable. OBJECTIVES: The aim of study was to estimate the probability rates for unbalanced offspring and to evaluate the risk for different categories of unfavorable pregnancy outcomes, depending on the size of chromosomal segment with differentiation between maternal/paternal origin of the reciprocal chromosomal translocations involving chromosome 7p (RCT-7p) and 7q (RCT-7q). In addition, the use of the obtained results has been illustrated by the example of a family with unique RCT t(7;9)(p21.3,p23). MATERIAL AND METHODS: Empirical and cytogenetic data on 341 pregnancies and offspring of 133 carriers were collected from 69 pedigrees of carriers of RCT-7p and RCT-7q at risk for a single 7 segment imbalance. The probability rates of particular form of pregnancy pathology have been calculated according to the method of Stengel-Rutkowski and Stene, including all forms of meiotic segregation and their survival rates after fertilization to term childbirth. RESULTS: The probability rates for unbalanced offspring for carriers of RCT-7p after 2:2 disjunction and adjacent-1 segregation were calculated as 5.5% +/- 2.2% (6/108); for maternal (MAT) and paternal (PAT) carriers were about < 1% (0/56) and 13.6 +/- 5.2% (6/44) (p = 0.04) respectively. Considering different segment lengths of 7p, the following values for shorter and longer segments were obtained: 23.0 +/- 11.7% (3/13) for 7p21-->pter; 3.3 +/- 3.3% (1/30) for 7p 14-->pter and 3.1 +/- 2.1% (2/65) for 7p 1-->pter The risk figures for stillbirth/earl neonatal death were estimated at 2.8 +/- 1.6% (3/108), but for miscarriage were calculated at 25.9 +/- 4.2% (28/108) for carriers RCT-7p. The probability rates for unbalanced offspring at birth for carriers of RCT-7q were calculated as 2.7 +/- 1.5% (3/111); for MAT and PAT carriers were 3.5 +/- 2.0% (3/86) and < 2.6% (0/19) respectively. Considering different segment lengths of 7q, the following values for shorter and longer segments were obtained: 6.2 +/- 6.1% (1/16) for 7q33-->qter; 5.3 +/- 3.6% (2/38) for 7q32-->qter and < 0.82% (0/57) for 7q11-->qter. The risk figures for stillbirth/early neonatal death were estimated at 9.9 +/- 2.8% (11/111), but for miscarriage were calculated at 34.2 +/-4.5% (38/111) for carriers RCT-7q. The probability estimated values for unbalanced fetuses, evaluated prenatally in the second trimester of pregnancy for carriers of RCT-7p and RCT-7q were similar i.e. 41.7 +/- 14.2% (5/12) and 46.7 +/-12.9% (7/15), respectively. CONCLUSIONS: 1. The probability rates for unbalanced offspring and the risk values for individual categories of unfavorable outcomes for carriers of RCT-7 are different and depend on the size of chromosome 7 segment involved in RCT 2. The probability rate for unbalanced offspring for paternal carriers of RCT-7p is higher than for maternal carriers (p = 0.04). 3. It is suggested that the probability rate for unbalanced offspring for maternal carriers of RCT-7q may be higher than for paternal carriers.

[Searching for Tourette's syndrome gene. Part 1. Heterogeneity of clinical phenotypes]. / W poszukiwaniu genu zespolu Gilles de la Tourette'a. Czesc 1. Róznorodnosc fenotypów klinicznych.

The French neuropsychiatrist Georges Gilles de la Tourette described in 1885 the "Maladie des Tics" which later was named after him, as Gilles de la Tourette syndrome (GTS). Gilles de la Tourette syndrome is a neurodevelopmental disorder characterized by simple and complex motor and vocal tics with multiple neuropsychiatric comorbidities. GTS is often concurrent with obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD). There are several clinical GTS subtypes: GTS only, GTS+OCD, and GTS+OCD+ADHD. Additional clinical aspects of the disorder include occurrence of anger episodes, anxiety and mood disorders, and learning and sleeping disturbances. The genetics of GTS is complex and remains unclear. So far, no causative candidate genes have been identified. However, segregation studies in families and twins with GTS provide strong evidence for the existence of a genetic background associated with a multifactorial mode of inheritance. Progress in studies on genome variability among patients with GTS is necessary to improve pharmacotherapeutic strategies of the disorder.

[Searching for Tourette's syndrome gene. Part 2. Patient's genome variability]. / W poszukiwaniu genu zespolu Tourette'a. Czesc 2. Zmiennosc genomu chorych.

Gilles de la Tourette syndrome (GTS) is a complex, heterozygous genetic disorder. Twenty chromosomal rearrangements (7q22-q31, 8q13-q22, and 18q22) indicating genomic regions which may be involved in the etiology of the disorder have been reported in families with GTS. Moreover, pathogenic mutations responsible for GTS were found in the SLITRK1 and the L-histidine decarboxylase (HDC) genes. The W317X mutation in the HDC gene points to a possible role for histaminergic neurotransmission in the mechanism and modulation of tic disorder. The distribution of single nucleotide polymorphisms (SNPs) was examined in at least 14 candidate genes (DRD1, DRD2, DRD3, DRD4, DAT1, MAOA, 5HTR2A, 5HTR3A, TDO2, CNR1, HLA-DRB, IL1RA, MOG, and SGCE) using a case-control genetic association analysis. Still, a lack of replicated and consistent results was observed. Recently, rare structural variants of different genes involved in neurodevelopment determined by recurrent exonic copy number variations (CNVs) have been found in a subset of patients suffering from GTS.

Wolf-Hirschhorn syndrome due to pure and translocation forms of monosomy 4p16.1 → pter.

The aim of this study was to obtain a quantitative definition of Wolf-Hirschhorn syndrome (WHS) through systematic phenotypic analyses in a group of six children with 4p15.32 → pter, 4p15.33 → pter, or 4p16.1 → pter monosomy (considered together as M4p16.1). These results were used for evaluation of the phenotypic effects of a double chromosome imbalance in one child with 4p16.1 → pter monosomy and additional 11q23.3 → qter trisomy. Children with pure M4p16.1 presented with a total of 227 clinical and morphological traits, of which 119 were positive in at least two of them. These traits overlap to a great extent with clinical criteria defining the WHS phenotype. Among the 103 traits identified in the child with unbalanced translocation der(4)t(4;11)(p16.1;q23.3), most clinical and developmental traits (but only 11 morphological) were found to be shared by WHS children with pure M4p16.1 and at least one reported patient with pure 11q trisomy. Forty-six traits of this child corresponded solely to those identified in at least one child with pure M4p16.1. Only five traits of the hybrid phenotype were present in at least one child with pure distal 11q trisomy but in none of the present children with pure M4p16.1. In conclusion, most of the morphological traits of the hybrid phenotype in the child with der(4)t(4;11)(p16.1;q23.3) can be attributed to the M4p16.1, whereas their overlap with those associated with pure distal 11q trisomy is less evident. Phenotype analyses based on the same systematic data acquisition may be useful in understanding the phenotypic effects of different chromosome regions in complex rearrangements. © 2011 Wiley-Liss, Inc.

[Genetic counseling in osteodystrophy Albright syndrome. Part I. Phenotypic diagnosis and pedigree analysis]. / Poradnictwo genetyczne w zespole osteodystrofii Albrighta, czyli rzekomej niedoczynnosci przytarczyc. Cz. I. Diagnoza fenotypowa i analiza rodowodowa.

In this article we describe problems of genetic counseling with features of morphological phenotype, biochemical and molecular changes observed in osteodystrophy Albright syndrome, inherited autosomal dominant condition.

[Genetic counseling in osteodystrophy Albright's syndrome. Part II. GNAS1 gene and encoded protein function, genetic forecast and treatment]. / Poradnictwo genetyczne w zespole osteodystrofii Albrighta, czyli rzekomej niedoczynnosci przytarczyc. Cz. II. Gen GNAS1 i funkcje kodowanego bialka, elementy prognozy genetycznej i mozliwosci leczenia.

In this article we describe localization and structure of genes from GNAS1 cluster, which mutations are responsible for characteristic group of features described mainly as Albright's syndrome. We present the capabilities of expressions of different phenotypes depending on types of molecular changes and possibilities of genetic prognosis with problems need to be solved in interdisciplinary support.

[To know more about the Prader-Willi syndrome. Diagnosis]. / Wiedziec wiecej o zespole Pradera-Williego. Diagnostyka.

Prader-Willi syndrome, induced by a function changes of paternal genes in the subcentrometric region of the chromosome 15 (q11.2q13), is the most common genetic cause of obesity resulting from hyperphagia. Behavioural disturbancies with compulsions in which psychiatric interventions are necessary, are relatively frequently seen. In this paper we reviewed the recent data of the clinical diagnosis verified by molecular studies.

[To know more about the Prader-Willi syndrome. Multidisciplinary support]. / Wiedziec wiecej o zespole Pradera-Williego. Opieka wielospecjalistyczna.

Prader-Willi syndrome, induced by a loss of function of paternal genes in the subcentrometric region of the chromosome 15 (q11.2q13), is a complex neurodevelopmental disorder with characteristic obesity resulting from hyperphagia. In addition behavioural disturbancies with obsessive-compulsive features, aggression, temper tantrums included, are relatively frequently seen and they often require psychiatric intervention. In this part of the paper we reviewed the recent data of behavioural phenotype the correlations of phenotype-genotype and possibilities of the multidisciplinary support for the affected persons and theirs families.

Chromosome (re)positioning in spermatozoa of fathers and sons - carriers of reciprocal chromosome translocation (RCT).

BACKGROUND: Non-random chromosome positioning has been observed in the nuclei of several different tissue types, including human spermatozoa. The nuclear arrangement of chromosomes can be altered in men with decreased semen parameters or increased DNA fragmentation and in males with chromosomal numerical or structural aberrations. An aim of this study was to determine whether and how the positioning of nine chromosome centromeres was (re)arranged in the spermatozoa of fathers and sons - carriers of the same reciprocal chromosome translocation (RCT). METHODS: Fluorescence in situ hybridization (FISH) was applied to analyse the positioning of sperm chromosomes in a group of 13 carriers of 11 RCTs, including two familial RCT cases: t(4;5) and t(7;10), followed by analysis of eight control individuals. Additionally, sperm chromatin integrity was evaluated using TUNEL and Aniline Blue techniques. RESULTS: In the analysed familial RCT cases, repositioning of the chromosomes occurred in a similar way when compared to the data generated in healthy controls, even if some differences between father and son were further observed. These differences might have arisen from various statuses of sperm chromatin disintegration. CONCLUSIONS: Nuclear topology appears as another aspect of epigenetic genomic regulation that may influence DNA functioning. We have re-documented that chromosomal positioning is defined in control males and that a particular RCT is reflected in the individual pattern of chromosomal topology. The present study examining the collected RCT group, including two familial cases, additionally showed that chromosomal factors (karyotype and hyperhaploidy) have superior effects, strongly influencing the chromosomal topology, when confronted with sperm chromatin integrity components (DNA fragmentation or chromatin deprotamination).

Genetic counseling in Robertsonian translocations der(13;14): frequencies of reproductive outcomes and infertility in 101 pedigrees.

Robertsonian translocations 13/14 are the most common chromosome rearrangements in humans. However, most studies aimed at determining risk figures are more than 20 years old. Their results are often contradictory regarding important topics in genetic counseling such as infertility and unfavorable pregnancy outcomes. Here, we present a study on a sample of 101 previously unreported pedigrees of der(13;14)(q10;q10). In order to minimize problems of partial ascertainment, we included families with a wide range of reasons of ascertainment such as birth of a child with congenital anomalies, prenatal diagnosis due to maternal age, fertility problems and recurrent pregnancy loss. No evidence of increased infertility rates of female and male carriers was found. The detected miscarriage frequency of female carriers was higher than previously reported (27.6 +/- 4.0% of all spontaneous pregnancies). This may be explained by an over-correction of earlier studies, which excluded all unkaryotyped miscarriages. In three out of 42 amniocenteses, translocation trisomies 13 were diagnosed (7.1 +/- 4.0% of all amniocenteses). The frequency of stillbirths was 3.3 +/- 1.6% for female carriers and 1.4 +/- 1.4% for male carriers. A low risk for the live birth of translocation trisomy 13 children was confirmed since no live born children with trisomy 13 or Pätau syndrome were detected in the ascertainment-corrected sample.

[Probability rates for different pregnancy outcomes in carriers of reciprocal chromosomal translocations involving chromosome 13]. / Prawdopodobienstwo wystapienia róznych patologii ciazy w rodzinach nosicieli translokacji chromosomowych wzajemnych angazujacych chromosom 13.

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.