Nieinwazyjny test NIFTY w diagnostyce najczęstszych trisomii chromosomowych u płodu

NIFTY (Non-invasive Fetal Trisomy Test) is a non-invasive prenatal test which is used for diagnosing fetal trisomy. The test is based on the analysis of cell free fetal DNA (cffDNA) present in the plasma and serum of a pregnant woman. NIFTY allows to detect fetal trisomy of chromosomes 13, 18, 21, X and Y and also X monosomy. Abnormal NIFTY results still need to be verified using other diagnostic techniques. However, the sensitivity of NIFTY for trisomy 21, 18 and 13 is estimated at 99%, 97% and 79% respectively, with false positive rate for all examined trisomies and X monosomy ofNIFTY (Noninvasive Fetal Trisomy test) jest nieinwazyjnym testem prenatalnym, który służy do diagnostyki trisomii u płodu. Test opiera się na analizie DNA płodu (cffDNA) obecnego w osoczu i surowicy kobiety ciężarnej. W chwili obecnej umożliwia wykrycie u płodu trisomii chromosomów 13, 18, 21, X i Y oraz monosomii chromosomu X. Wyniki nieprawidłowe uzyskane za pomocą testu NIFTY wciąż jeszcze muszą być weryfikowane przy użyciu innych technik diagnostycznych, niemniej czułość testu dla trisomii 21 ocenia się na 99%, dla trisomii 18 na 97% a trisomii 13 na 79%, zaś odsetek wyników fałszywie dodatnich dla wszystkich badanych trisomii i monosomii X mieści się poniżej 1%. Obecnie NIFTY jest dostępny w Polsce odpłatnie, stosowany, jako dobre badanie przesiewowe dla trisomii, które wykonuje się obok badania USG i testów biochemicznych, w przypadku niepokoju pacjentki, a także w sytuacji, gdy pacjentka nie decyduje się na wykonanie diagnostyki inwazyjnej. Czułość i specyficzność NIFTY zapewne będą ulegały poprawie w miarę doskonalenia metody oraz przeprowadzenia badań na dostatecznie dużej grupie pacjentek, dlatego test ten w niedalekiej przyszłości ma szansę stać się podstawowym testem diagnostycznym dla najczęstszych trisomii, pozwalającym na rezygnację z badań inwazyjnych zlecanych w tym kierunku. Z dużym prawdopodobieństwem cffDNA uzyskiwany z surowicy kobiety ciężarnej będzie także wykorzystywane w diagnostyce zmian strukturalnych i genowych u płodu. Celem pracy jest przedstawienie nowej metody diagnostycznej

Non-invasive prenatal test in the diagnosis of aneuploidy 13, 18 and 21 – theoretical and practical aspects

Abstract The incidence of numerical chromosome aberrations is about 5% during the entire pregnancy, and about 0.2% in live-born infants. Most commonly observed numerical aberrations in live births are trisomies of chromosomes 13, 18, 21, X and Y and monosomy of the X chromosome. It is estimated that approximately 70-80% of newborns with aneuploidies are born by women who did not present obvious risk factors, therefore, according to a recent recommendation by PTG, prenatal diagnosis increasing the detection of fetal aneuploidy should be offered to the entire population of women. Due to the risk of complications associated with invasive tests and a large number of unnecessarily performed tests of this type, it is postulated that invasive diagnostics should be used in very specific cases, and a non-invasive diagnostics should have a screening character. Non-invasive diagnostics include: 1) detailed ultrasonography performed in 11-13(+6 days) hbd and in 18-24 hbd; 2) biochemical tests: PAPP-A (first-trimester test) and the triple test (second-trimester test) and less frequently performed: double, quadruple, and integrated tests. High detection rate of chromosomal aberrations in non-invasive tests (at least 75%, with no more than 5% risk of obtaining false positive results) and lack of procedure-related pregnancy losses constitute the advantage of noninvasive prenatal diagnosis

Prenatal diagnosis--principles of diagnostic procedures and genetic counseling.

The frequency of inherited malformations as well as genetic disorders in newborns account for around 3-5%. These frequency is much higher in early stages of pregnancy, because serious malformations and genetic disorders usually lead to spontaneous abortion. Prenatal diagnosis allowed identification of malformations and/or some genetic syndromes in fetuses during the first trimester of pregnancy. Thereafter, taking into account the severity of the disorders the decision should be taken in regard of subsequent course of the pregnancy taking into account a possibilities of treatment, parent's acceptation of a handicapped child but also, in some cases the possibility of termination of the pregnancy. In prenatal testing, both screening and diagnostic procedures are included. Screening procedures such as first and second trimester biochemical and/or ultrasound screening, first trimester combined ultrasound/biochemical screening and integrated screening should be widely offered to pregnant women. However, interpretation of screening results requires awareness of both sensitivity and predictive value of these procedures. In prenatal diagnosis ultrasound/MRI searching as well as genetic procedures are offered to pregnant women. A variety of approaches for genetic prenatal analyses are now available, including preimplantation diagnosis, chorion villi sampling, amniocentesis, fetal blood sampling as well as promising experimental procedures (e.g. fetal cell and DNA isolation from maternal blood). An incredible progress in genetic methods opened new possibilities for valuable genetic diagnosis. Although karyotyping is widely accepted as golden standard, the discussion is ongoing throughout Europe concerning shifting to new genetic techniques which allow obtaining rapid results in prenatal diagnosis of aneuploidy (e.g. RAPID-FISH, MLPA, quantitative PCR)

Rapid-FISH – fast and reliable method of detecting common numerical chromosomal aberrations in prenatal diagnosis

Abstract Objective: In recent years, new possibilities of prenatal diagnosis have opened up, due to the development of techniques which guarantee shorter time of obtaining results. One of those methods, called Rapid-FISH (rapid fluorescence in situ hybridization), for detecting numerical aberrations of chromosomes 13, 18, 21, X and Y without culturing, enables to have the results in 2-5 days. The time necessary to obtain fetal karyotype result with the usage of the classical cytogenetic methods is about 2-3 weeks and depends mainly on the culture growth rate. Design: The aim of the study was to evaluate the effectiveness of the Rapid-FISH technique in detecting numerical chromosome aberrations of 13, 21, 18, X and Y in amniocytes’ nuclei from amniotic fluid. Materials and Methods: Rapid-FISH and cytogenetic analysis has been performed for 161 pregnancies in the Department of Genetics at Wroclaw Medical University during years 2005 and 2006. The FISH was performed using AneuVysion kit (Vysis), according to a standard protocol. Results: All normal and abnormal results were confirmed by classical cytogenetic method (GTG banding and karyotyping). Additional chromosomal aberrations, not possible to be detected in FISH, were observed in case of two patients with normal results from FISH analysis. Conclusions: Rapid-FISH is a reliable and fast method for detecting numerical chromosomal aberrations in prenatal diagnosis and should be implemented as a routine diagnostic procedure in pregnancies with high risk of fetal aneuploidy (of chromosomes 13, 18, 21, X i Y)

The role of genetic counselling in oncology

All cancers are genetic disorders, but not all genetic disorders are inherited. Most cancers are sporadic, independent events that do not affect other family members. There is a population risk of developing any cancer and it mainly depends on the individual’s age and environmental factors. Cancers linked to predisposition syndromes constitute about 5–10% of all cancer cases. Although it is a small group, making the right diagnosis is important, because of the consequences to the individual, his/her relatives and the benefits they can acquire from surveillance, early therapy and/ or surgical interventions. Genetic counselling plays an important role in diagnosing cancer predisposition syndromes. Hereditary cancer risk assessment includes evaluation of personal and family history, as well as other medical and environmental risk factors. Indications for genetic testing, scope of tests, possible results and their consequences for the patient and his/her family should be discussed

The role of genetic counselling in oncology

All cancers are genetic disorders, but not all genetic disorders are inherited. Most cancers are sporadic, independent events that do not affect other family members. There is a population risk of developing any cancer and it mainly depends on the individual’s age and environmental factors. Cancers linked to predisposition syndromes constitute about 5–10% of all cancer cases. Although it is a small group, making the right diagnosis is important, because of the consequences to the individual, his/her relatives and the benefits they can acquire from surveillance, early therapy and/ or surgical interventions. Genetic counselling plays an important role in diagnosing cancer predisposition syndromes. Hereditary cancer risk assessment includes evaluation of personal and family history, as well as other medical and environmental risk factors. Indications for genetic testing, scope of tests, possible results and their consequences for the patient and his/her family should be discussed

Prenatal diagnosis--principles of diagnostic procedures and genetic counseling.

The frequency of inherited malformations as well as genetic disorders in newborns account for around 3-5%. These frequency is much higher in early stages of pregnancy, because serious malformations and genetic disorders usually lead to spontaneous abortion. Prenatal diagnosis allowed identification of malformations and/or some genetic syndromes in fetuses during the first trimester of pregnancy. Thereafter, taking into account the severity of the disorders the decision should be taken in regard of subsequent course of the pregnancy taking into account a possibilities of treatment, parent's acceptation of a handicapped child but also, in some cases the possibility of termination of the pregnancy. In prenatal testing, both screening and diagnostic procedures are included. Screening procedures such as first and second trimester biochemical and/or ultrasound screening, first trimester combined ultrasound/biochemical screening and integrated screening should be widely offered to pregnant women. However, interpretation of screening results requires awareness of both sensitivity and predictive value of these procedures. In prenatal diagnosis ultrasound/MRI searching as well as genetic procedures are offered to pregnant women. A variety of approaches for genetic prenatal analyses are now available, including preimplantation diagnosis, chorion villi sampling, amniocentesis, fetal blood sampling as well as promising experimental procedures (e.g. fetal cell and DNA isolation from maternal blood). An incredible progress in genetic methods opened new possibilities for valuable genetic diagnosis. Although karyotyping is widely accepted as golden standard, the discussion is ongoing throughout Europe concerning shifting to new genetic techniques which allow obtaining rapid results in prenatal diagnosis of aneuploidy (e.g. RAPID-FISH, MLPA, quantitative PCR)

Prenatal Versus Postnatal Diagnosis of Meckel–Gruber and Joubert Syndrome in Patients with TMEM67 Mutations

Renal cystic diseases are characterized by genetic and phenotypic heterogeneity. Congenital renal cysts can be classified as developmental disorders and are commonly diagnosed prenatally using ultrasonography and magnetic resonance imaging. Progress in molecular diagnostics and availability of exome sequencing procedures allows diagnosis of single-gene disorders in the prenatal period. Two patients with a prenatal diagnosis of polycystic kidney disease are presented in this article. TMEM67 mutations were identified in both fetuses using a whole-exome sequencing (WES) study. In one of them, the phenotypic syndrome diagnosed prenatally was different from that diagnosed in the postnatal period

Prenatal Diagnosis of Jeune Syndrome Caused by Compound Heterozygous Variants in DYNC2H1 Gene—Case Report with Rapid WES Procedure and Differential Diagnosis of Lethal Skeletal Dysplasias

Skeletal dysplasias (SDs) are a large, heterogeneous group of mostly genetic disorders that affect the bones and cartilage, resulting in abnormal growth and development of skeletal structures. The high clinical and genetic diversity in SDs cause difficulties in prenatal diagnosis. To establish a correct prognosis and better management, it is very important to distinguish SDs with poor life-limiting prognosis or lethal SDs from other ones. Bad prognosis in foetuses is assessed on the basis of the size of the thorax, lung volumes, long bones’ length, bones’ echogenicity, bones’ angulation or presented fractures, and the concomitant presence of non-immune hydrops or visceral abnormalities. To confirm SD diagnosis and perform family genetic consultation, rapid molecular diagnostics are needed; therefore, the NGS method using a panel of genes corresponding to SD or whole-exome sequencing (WES) is commonly used. We report a case of a foetus showing long bones’ shortening and a narrow chest with short ribs, diagnosed prenatally with asphyxiating thoracic dystrophy, also known as Jeune syndrome (ATD; OMIM 208500), caused by compound heterozygous variants in the DYNC2H1 gene, identified by prenatally performed rapid-WES analysis. The missense variants in the DYNC2H1 gene were inherited from the mother (c.7289T>C; p.Ile2430Thr) and from the father (c.12716T>G; p.Leu4239Arg). The DYNC2H1 gene is one of at least 17 ATD-associated genes. This disorder belongs to the ninth group of SD, ciliopathies with major skeletal involvement. An extremely narrow, bell-shaped chest, and abnormalities of the kidneys, liver, and retinas were observed in most cases of ATD. Next to lethal and severe forms, clinically mild forms have also been reported. A diagnosis of ATD is important to establish the prognosis and management for the patient, as well as the recurrence risk for the family