A group of 63 families from the Pomerania-Kujawy region were analyzed for three BRCA1 gene Polish founder mutations, 5382insC, 300T>G, and 4153delA, because of breast (BrCa) and/or ovarian cancer (OvCa) history. The analysis was carried out by multiplex polymerase chain reaction method. BRCA1 mutation was revealed in nine (14%) families: in three (33%) of hereditary BrCa and OvCa families, in three (8%) of hereditary BrCa families, and in three (21%) of hereditary OvCa families. According to risk criteria, it was revealed in 45% of high-risk families with more than three cancers, 13% of moderate-risk families with two cancers, and 8% of families with sporadic OvCa. In six families, the mutation was found in a proband with BrCa or OvCa and in three families, the mutation was found in a healthy proband, first-degree relative of a patient deceased of BrCa or OvCa. 5382insC frameshift mutation accounted for 67% and 300T>G missense mutation for 33% of all identified familial mutations. 4153delA frameshift mutation was not found in analyzed sample of families. 5382insC mutation was found in 9% and 300T>G in 5% of all investigated families, and in 27 and 18%, respectively, of high-risk families. This underlines the importance of applying strict inclusion criteria to analyze mutation frequency in hereditary BrCa/OvCa families.
Background The 3q duplication syndrome is a result of duplication of a large fragment of the long arm of chromosome 3, mainly 3q21-qter, and in most cases it is diagnosed only after birth. The phenotypic consequences resulting from genetic imbalance are an important source of information for genetic counselling, especially in prenatal diagnostics. However, in most cases it is impossible to define them precisely because the final clinical presentation is a result of an overlap, usually due to different sizes of deletions and/or duplications not only chromosome 3 but also of translocation partner chromosome. In this article, we present a prenatal diagnosis of the 3q duplication syndrome in a foetus, arising from a balanced insertion ins (7,3)(q21.2;q12.3q29) carried by the mother. Case presentation The article presents a case of a 29-year-old woman referred to the Genetic Outpatient Clinic for consultation in the 12th week of her fifth pregnancy with a diagnosis of generalised hydrops foetalis. The analysis of karyotype using GTG technique and FISH allowed diagnosis of a balanced aberration in the mother, and determined the type of chromosomal rearrangement, which allowed the identification of the origin of the additional genetic material in the foetus and the previous malformed child of the same couple. The use of molecular karyotyping techniques (FISH and aCGH) allowed a precise determination of the size of the imbalanced fragments in the affected siblings. Conclusions The aCGH technique is particularly valuable for the diagnostics of submicroscopic deletions and duplications, if no imbalanced chromosomal aberrations are detected by routine cytogenetic tests. It is also a valuable technique for identifying and fully characterizing genetic material of unknown origin, which can’t be identified using routine cytogenetic techniqes. However, it does not allow identification of balanced aberrations in carriers.
BackgroundGermline mutations of the CHEK2 gene have been reported to be associated with breast cancer. In this study, we analyzed the association of CHEK2 mutations with the risk of development of breast cancer in women of North-Central Poland.Methods420 women with breast cancer and 435 controls were tested for three protein truncating (IVS2 + 1G > A, 1100delC, del5395) and one missense (I157T) CHEK2 mutation. IVS2 + 1G > A and I157T mutations were identified by RFLP-PCR, 1100delC variant was analyzed using an ASO-PCR and del5395 mutation by multiplex-PCR. The statistical tests: the odds ratio (OR) and Fisher’s exact test were used.ResultsIn 33 out of 420 (7.9%) women consecutively diagnosed with breast cancer, we detected one of four analyzed CHEK2 mutations: I157T, 1100delC, IVS2 + 1G > A or del5395. Together they were not associated with the increased risk of breast cancer (North-Central control group: OR = 1.6, p = 0.124; the general Polish population: OR = 1.4, p = 0.109). This association was only seen for IVS2 + 1G > A mutation (OR = 3.0; p = 0.039). One of the three truncating CHEK2 mutations (IVS2 + 1G > A, 1100delC, del5395) was present in 9 of 420 women diagnosed with breast cancer (2.1%) and in 4 of 121 women (3.3%) with a history of breast cancer in a first- and/or second- degree relatives. Together they were associated with the increased risk of disease in these groups, compared to the general Polish population (OR = 2.1, p = 0.053 and OR = 3.2; p = 0.044, respectively). I157T mutation was detected in 25 of 420 women diagnosed with breast cancer (6.0%) and in 8 of 121 women (6.6%) with a history of breast cancer in first- and/or second- degree relatives. The prevalance of I157T mutation was 4.1% (18/435) in North-Central control group and 4.8% (265/5.496) in the general Polish population. However it was not associated with an increased risk of breast cancer.ConclusionObtained results suggest that CHEK2 mutations could potentially contribute to the susceptibility to breast cancer. The germline mutations of CHEK2, especially the truncating ones confer low-penetrance breast cancer predisposition that contribute significantly to familial clustering of breast cancer at the population level.
Bardet Biedl Syndrome (BBS) is a rare, genetically determined syndrome which can result from a mutation in one of 19 known genes (often called BBS complex), which play a vital role in building structures and cell functions of cilia. Phenotypic symptoms of the syndrome usually progress in the first decade of life, however, they are characterized by a high diversity which makes their diagnosis difficult, especially in the early stage of life. The diagnosis is most frequently based on clinical symptoms and established in late childhood or adult life. BBS is a disorder of the non-motile cilia, which play the role of antennae receiving and transmitting sensory signals to photoreceptors of the retina, hearing cells or olfactory cells. Clinical symptoms of the disorders affecting these structures are: retinal pigmentary degeneration, polydactyly, learning difficulties, and formation of kidney, liver and pancreas cysts. The inheritance mode of BBS is in 80% autosomal recessive, which is connected with both parents carrying a mutated allele, and usually only giving birth to a symptomatic child defines a family as being at genetic risk, whith 25% risk of having another child with the disease and 50% of having offspring that are asymptomatic carriers For families with an identified mutation there exists a possibility of conducting prenatal or preimplementation genetic diagnosis in subsequent pregnancies The article presents a case of a patient in whom prenatal ultrasonography and subsequent clinical trials in post-natal period resulted in a Bardet-Biedl syndrome diagnosis, which was later confirmed through molecular tests.
BackgroundBalanced 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.ResultsThe 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.DiscussionDue 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.
Background: Allergy is associated with the loss of tolerance of environmental antigens, combined with a pathological immune response. There were no studies up to date that would show whether the quality of semen decreases in people with allergic diseases. Material and methods: The research included men who reported to the Gynecological Outpatient Clinic due to reproductive difficulties, defined as the lack of pregnancy after one year of regular intercourse. Semen quality was assessed according to the World Health Organization (WHO) standard. All patients underwent skin prick tests with the most important inhalation allergens (such as hazel, silver birch, mugwort, rye, dog, cat, Dermatophagoides farinae, Dermatophagoides pteronyssinus, alder, Alternaria alternata, Cladosporium herbarum, and grass mix). The data was statistically analyzed. Results: Results of 52 patients aged 25–52 years (34.62 ± 4.96) were analyzed. The mean BMI (Body mass index) was 28.25 (+ −3.77). It was found that 38 men (73%) had increased body weight, and 14 men (26.9%) were obese (BMI > = 30). 13 patients were smokers (25%), and 24 patients (46%) had skin tests positive for at least one inhaled allergen. Sperm tail defects were statistically more significant in patients allergic to birch, rye, cat, alder, and grass. In patients allergic to Alternaria alternata, head defects were statistically more significant ( p < .05). No association was found between allergy to house dust mites, mugwort, hazel, and dogs and the deterioration of semen. Conclusion: Allergy due to inhalation allergens had an influence on the quality of male semen. Further research is necessary to establish the immunological bases of this phenomenon.
BackgroundBalanced reciprocal chromosomal translocations (RCTs) are the ones of the most common structural aberrations in the population, with an incidence of 1:625. RCT carriers usually do not demonstrate changes in phenotype, except when the translocation results in gene interruption. However, these people are at risk of production of unbalanced gametes during meiosis, as a result of various forms of chromosome segregation. This may cause infertility, non-implantation of the embryo, shorter embryo or foetus survival, as well as congenital defects and developmental disorders in children after birth.The increasing popularity of cytogenetic molecular techniques, such as microarray-based CGH (aCGH), contributed to the improved detection of chromosomal abnormalities in patients with intellectual disability, however, these modern techniques do not allow the identification of the balanced in potential carriers. Therefore, classical chromosome analysis with GTG technique still plays an important role in the identification of balanced rearrangements in every case of procreation failure.Case presentationIn this article, a family with multiple occurrences of 17p13.3 duplication syndrome in the offspring and multiple miscarriages resulting from carrying of the balanced reciprocal translocation t(7;17)(p22;p13.2) by proband father is presented.The aCGH diagnostics allowed the identification of an unbalanced fragment responsible for the occurrence of clinical signs in the female patient, while karyotyping and FISH using specific probes allowed the localization of the additional material in the patient chromosomes, and identified the type of this translocation in the carriers.ConclusionsIdentification of a balanced structural aberration in one of the partners allows direct diagnostics for the exclusion or confirmation of genetic imbalance in the foetus via traditional invasive prenatal diagnostics. It is also possible to use an alternative method, Preimplantation Genetic Diagnosis (PGD) after in vitro fertilization, which prevents initiating pregnancy if genetic imbalance is detected in the embryo.
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