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.

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.

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.

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

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 â†’ pter and pure trisomy 19p13.3 â†’ 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 â†’ pter with monosomy 4p15.32 â†’ 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 â†’ 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 â†’ pter together with trisomy 19p13.3 â†’ pter as a double segment imbalance in children with WHS may be connected with a limited survivability in infancy.

Complex balanced chromosomal translocation t(2;5;13) (p21;p15;q22) in a woman with four reproductive failures.

BACKGROUND: Balanced complex translocations (BCTs) are rare events, they may result in reproductive failures: spontaneous abortions, missed abortions, stillbirths, congenital malformations in children, and male infertility. BCTs belong to the group of complex chromosome rearrangements (CCRs) - up to date about 260 cases were described. RESULTS: The described patient and her husband were referred to genetic counseling clinic because of four reproductive failures. GTG-banded chromosome analysis revealed presence of apparently balanced complex translocation t(2;5;13), which was verified and confirmed by molecular cytogenetics with single copy probes. This complex aberration was most likely responsible for reproductive failures in our patient. Since no high resolution molecular karyotyping (microarrays) was used, this rearrangement can only be considered to be balanced at cytogenetic level. DISCUSSION: Due to small number of reported cases of CCRs/BCTs and individual as well as unique character of such rearrangements, genetic counseling for CCRs carriers is complex and requires detailed pedigree analysis, as well as extended clinical and genetic testing.

Recurrence risks for different pregnancy outcomes and meiotic segregation analysis of spermatozoa in carriers of t(1;11)(p36.22;q12.2).

Cumulative data obtained from two relatively large pedigrees of a unique reciprocal chromosomal translocation (RCT) t(1;11)(p36.22;q12.2) ascertained by three miscarriages (pedigree 1) and the birth of newborn with hydrocephalus and myelomeningocele (pedigree 2) were used to estimate recurrence risks for different pregnancy outcomes. Submicroscopic molecular characterization by fluorescent in situ hybridization (FISH) of RCT break points in representative carriers showed similar rearrangements in both families. Meiotic segregation patterns after sperm analysis by three-color FISH of one male carrier showed all possible outcomes resulting from 2:2 and 3:1 segregations. On the basis of empirical survival data, we suggest that only one form of chromosome imbalance resulting in monosomy 1p36.22→pter with trisomy 11q12.2→qter may be observed in progeny at birth. Segregation analysis of these pedigrees was performed by the indirect method of Stengel-Rutkowski and showed that probability rate for malformed child at birth due to an unbalanced karyotype was 3/48 (6.2±3.5%) after ascertainment correction. The risk for stillbirths/early neonatal deaths was -/48 (<1.1%) and for miscarriages was 17/48 (35.4±6.9%). However, the probability rate for children with a normal phenotype at birth was 28/48 (58.3±7.1%). The results obtained from this study may be used to determine the risks for the various pregnancy outcomes for carriers of t(1;11)(p36.22;q12.2) and can be used for genetic counseling of carriers of this rearrangement.

[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.

[Influence of functional status of ovaries on results of controlled ovarian hyperstimulation]. / Wplyw stanu czynnosciowego jajników na wyniki kontrolowanej hiperstymulacji hormonalnej.

UNLABELLED: The controlled ovarian hyperstimulation is an integral part of infertility treatment. Its main objective is to obtain oocytes with a highest developmental potential. The stimulation protocols involving the gonadotropin-releasing hormone analogues and gonadotropins are considered as the most efficient. Despite many years of use, some aspects of controlled ovarian stimulation has not yet been clarified, especially the role of the functional status of ovaries before hormonal stimulation. The aim of study was to assess the influence of the functional status of ovaries on the results of the controlled ovarian hyperstimulation. MATERIALS AND METHODS: The retrospective study included female patients suffering from infertility The patients were divided into two groups depending on ultrasonographic appearance of ovaries before controlled ovarian hyperstimulation. The patients with small antral follicles < 6 mm in diameter were selected into group I. The patients with five or more antral follicles > or = 8 mm in diameter in each ovary were included into group II. The patients from both groups underwent similar treatment process. The major area of interest was the number, type and quality of oocytes obtained from patients from both groups after ovarian puncture. RESULTS: A retrospective study was conducted on 635 infertile patients (group I 382, group II 253). Altogether, 4055 oocytes were obtained in the group I and 2555 oocytes in the group II. The mean number of MII oocytes in group I was 9,2 and 8,7 in group II; p < 0.05. There were significantly more MI oocytes in group I than II. The mean numbers of immature oocytes were comparable between groups. The athretic and dysmorphic oocytes were more prevalent in group II. CONCLUSIONS: The results of the present study indicates that the functional status of ovaries before controlled ovarian hyperstimulation plays pivotal role for the treatment outcome.

[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.

[Systemic sclerosis. Part 1: searching for genetic determinants]. / Twardzina ukladowa. Czesc 1: poszukiwanie genetycznych uwarunkowan.

Familial aggregation of systemic sclerosis observed in the 1970 of twenty century, the presence of karyotype instability and chromosomal mosaicism and positive associations of certain polymorphisms of genes located in specific regions of the human genome may indicate the important contribution of genetic factors in the development and progression of the disease. The purpose of this paper is to present data on genetic changes found in scleroderma. Despite the enormous progress of research it is not yet clear, which disturbances in a specific way determine onset and development of the disease and which are non-specific forms of molecular abnormalities also present in other diseases with similar clinical symptoms.

[Thrombosis in the course of ovarian hyperstimulation syndrome]. / Zespól Hiperstymulacyjny Powiklany Zakrzepica.

A 28-year-old woman sought medical advice in the gynecology department because of infertility. Based on the results of the infertility workup, it was decided to apply in vitro fertilization treatment in her case. On the 12th day after embryo transfer, the patient was admitted to hospital because of nausea, vomiting, abdominal distention, and difficulties in breathing. The diagnosis was early pregnancy and the ovarian hyperstimulation syndrome (OHSS). After conservative treatment, the OHSS symptoms disappeared, and she was discharged in a good condition. However, nine days later the patient was readmitted due to a dull pain in her left shoulder, radiating onto the neck and left arm. Ultrasound examination revealed a thrombotic clot at the junction of the left external jugular vein and subclavian vein. Treatment with low-molecular-weight heparin was initiated. After 21 days of medication, the patient's symptoms resolved and, further, her pregnancy continued without complications. Although thromboembolic events are not frequently encountered in the course of OHSS, prophylactic anticoagulant therapy should be considered in all such patients.

[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.

[The results of cytogenetic and molecular genetic examinations in 35 couples with primary sterility]. / Wyniki badan cytogenetycznych i molekularnych u 35 par z nieplodnoscia pierwotna.

UNLABELLED: The causes of primary sterility are complex and frequently difficult to elucidate. Cytogenetic anomalies are responsible for sterility in 5-10% infertile couples. OBJECTIVES: Analysis of genetic background of primary sterility in 35 infertile couples. MATERIALS AND METHODS: 72h cultures of peripheral blood lymphocytes, GTG and CBG banding, fluorescence in situ hybrydization (FISH) with whole chromosome painting (WCP) probes. Karyotype analysis was performed in each patient out of 35 infertile couples referred to genetic counsel. SRY and CFTR gene mutation analysis by PCR was performed in all men with abnormal sperm. RESULTS: Chromosome aberrations were found in 6 couples. Klinefelter syndrome (47,XXY) was disclosed in 2 men. Isochromosome i(Xq) was found in 1 woman. The structural balanced translocations were found in 2 men; t(15;16)(q13;p13.3), t(1;19)(p35;q13.3) and a robertsonian translocation t(14;21)(q10;q10) in one. All men with chromosome aberrations had sperm anomalies: oligozoospermia, astenozoospermia, cryptozoospermia or azoospermia. There was a CFTR mutation, deltaF508, in one man and no SRY mutation in molecularly examined men with sperm abnormalities. CONCLUSIONS: In couples with primary sterility mainly the men are carriers of chromosome aberrations (CA). Because of 17.14% risk of the presence of chromosome aberrations in these couples, cytogenetic analysis should be an obligatory element of infertility diagnosis.

Genetic counselling in carriers of reciprocal chromosomal translocations involving short arm of chromosome X.

A central concept in genetic counselling is the estimation of the probability of occurrence of unbalanced progeny at birth and other unfavourable outcomes of pregnancy (miscarriages, stillbirths and early death). The estimation of the occurrence probability for individual carriers of four different X-autosome translocations with breakpoints at Xp, namely t(X;5)(p22.2;q32), t(X;6)(p11.2;q21), t(X;7)(p22.2;p11.1), and t(X;22)(p22.1;p11.1), is presented. The breakpoint positions of chromosomal translocations were interpreted using GTG, RBG and FISH-wcp. Most of these translocations were detected in women with normal phenotype, karyotyped because of repeated miscarriages and/or malformed progeny. A girl with very rare pure trisomy Xp22.1-->pter and a functional Xp disomy was ascertained in one family and her clinical picture has been described in details. It has been suggested that not fully skewed X chromosome inactivation of X-autosome translocation with breakpoint positions at Xp22 (critical segment) could influence the phenotype and risk value. Therefore, the X inactivation status was additionally evaluated by analysis of replication banding patterns using RBG technique after incorporation of BrdU. In two carriers of translocations: t(X;5)(p22.2;q32) and t(X;7)(p22.2;p11.1), late replication state of der(X) was observed in 5/100 and 10/180 analysed cells, respectively. In these both cases the breakpoint positions were clustered at the critical segment Xp22.2. In two other cases, one with the breakpoint position within [t(X;22)(p22.1;p11.1)] and one outside the critical region [t(X;6)(p11.2;q21)], fully skewed inactivation was seen. Therefore, we suggest that neither the distribution of the breakpoint positions nor fully skewed inactivation influenced the phenotype of observed t(X;A) carriers. The occurrence probabilities of the unbalanced progeny were calculated according to Stene and Stengel-Rutkowski along with application of updated available empirical data. In the studied group the values of occurrence probability for unbalanced offspring at birth ranged from 2.1% to 17%. Information on the magnitude of the individual figures may be important for women carrying a reciprocal X;A translocation when deciding upon further family planning.

Interstitial deletion 9q22.32-q33.2 associated with additional familial translocation t(9;17)(q34.11;p11.2) in a patient with Gorlin-Goltz syndrome and features of Nail-Patella syndrome.

The phenotype of Gorlin-Goltz syndrome or basal cell nevus syndrome (BCNS, #109400, OMIM), a Mendelian trait due to PTCH mutations has been reported in a few cases of interstitial deletion of chromosome 9q. We present an 11-year-old girl with clinical features consistent with BCNS including bridging of sella turcica, biparietal bossing, downward slanting palpebral fissures, mandible prognathism, pectus excavatum, thumb abnormalities, occult spina bifida at L5-S4, numerous basal cell nevi, and single basal cell carcinoma. Cytogenetic analysis using high-resolution banding techniques and fluorescence in situ hybridization (FISH) revealed interstitial chromosome deletion 9q22.32-q33.2 involving the PTCH gene as a secondary breakage event to a chromosome translocation t(9;17)(q34.1;p11.2)mat. Further FISH studies showed the translocation breakpoint on 9q34.11 maps proximal to ABL, between the BAC clone RP11-88G17 and the LMX1B gene. The latter gene encodes a transcription factor, in which loss of function mutations are responsible for the nail-patella syndrome (NPS, #161200 OMIM). Interestingly, some features of our proband (e.g., bilateral patellar dysplasia and abnormal clavicular shape), as well as her healthy sister who carries the same translocation, are also found in patients with NPS. The chromosome 17p11.2 breakpoint maps in the Smith-Magenis syndrome common deletion region, within two overlapping BAC clones, CTD-2354J3 and RP11-311F12.