Karyotype Analysis

Either amniocentesis or CVS can provide fetal cells for karyotyping. Preparation and analysis of chromosomes from cultured amniotic fluid cells or cultured chorionic villi require 10 to 14 days, although chorionic villi can also be used for karyotyping after short- term incubation. This short- term incubation using rapid metaphase analysis of villous cytotrophoblast tissue provides a result more quickly, but it has lower resolution and a higher rate of mosaicism that can render interpretation difficult. With long- term culture, the cultured cells from which the karyotype is obtained come from the mesenchymal core of the villus (see Fig. 1), which is embryologically more closely related to the developmental lineages that give rise to the fetus. Some laboratories use both techniques, but if only one is used, long- term culture is therefore the technique of choice. The resolution of chromosome spreads prepared from prenatal samples is lower than from other tissues, but seg mental abnormalities of 7 to 10 Mb and larger should be readily visible, depending on the region involved.

Fig1. Development of the tertiary chorionic villi and placenta. (A) Cross-section of an implanted embryo and placenta at ~21 days. (B) Cross section of a tertiary villus showing establishment of circulation in mesenchymal core, cytotrophoblast, and syncytiotrophoblast. (From Moore KL: The developing human: Clinically oriented embryology, ed 4, Philadelphia, 1988, WB Saunders.)

Chromosomal abnormalities are detected in 10% to 30% of pregnancies with fetal congenital anomalies, and this number is higher when multiple malformations are present. The karyotypes most often seen in fetuses ascertained by abnormal ultrasonographic findings are the common autosomal trisomies (21, 18, and 13) and 45,X (Turner syndrome). The presence of a cystic hygroma is associated with aneuploidy in more than 50% of cases, most commonly 45,X, but it can also occur in Down syndrome and trisomy 18, or in fetuses with normal karyotypes.

Fluorescence In Situ Hybridization

 Fluorescence in situ hybridization (FISH) makes it possible to rapidly screen interphase nuclei in fetal cells for the common aneuploidies of chromosomes 13, 18, 21, X, and Y immediately after amniocentesis or CVS, with a result available usually in 1 to 2 days. This can be useful when rapid information is needed if time- sensitive decisions regarding pregnancy management and delivery planning could be affected by a trisomy diagnosis (e.g., when a growth- restricted fetus is suspected to have trisomy 18). Because FISH only provides limited information, it should always be followed by a more definitive test, karyotype, or CMA. Although still offered, FISH is now less commonly used because CMA can provide more definitive results with only a slightly longer turnaround time of 5 to 7 days. In some countries outside the United States, rapid aneuploidy testing on CVS or amniotic fluid samples is done by quantitative polymerase chain reaction (PCR) amplification of unique regions on chromosomes 13, 18, and 21.

Chromosomal Microarray Analysis

CMA is increasingly replacing karyotyping for prenatal diagnosis. Copy number variants (CNVs), including chromosomal aneuploidy and seg mental imbalances, such as duplications, triplications, deletions, or marker chromosomes, can be detected at much higher resolution by CMA than can be accomplished even with high- resolution karyotyping. Although ACOG has advised that CMA, rather than karyotyping, should be the first- line test when a fetal abnormality is detected by ultrasonography and recommends that all women having invasive testing be given the option to have CMA, the Society of Obstetricians and Gynaecologists of Canada still recommends CMA as a second- tier test following a normal karyotype.

For some findings a karyotype is still needed (e.g., to determine whether a copy number gain for chromosome 21 is the result of a trisomy or an unbalanced robertsonian translocation). CMA also does not detect balanced translocations and balanced inversions, but these are more rarely the cause of fetal congenital anomalies or syndromes. The current data support that a prenatal CMA can identify a clinically significant CNV about 1% to 1.7% of the time, and when a CMA is done for fetal congenital anomalies this number goes up to 6% to 7% overall and to over 10% when there are multiple con genital anomalies. About 1% to 2% of the time CMA can identify variants of uncertain significance (VUS), or findings that indicate presence of a condition in the fetus that was not suspected. These can make counseling com plex and are discussed in more detail later.

Sequencing to Detect Chromosomal Abnormalities

Some laboratories outside the United States are beginning to use low- coverage whole genome sequencing with counting of fragments aligned to each chromosome to determine the copy number of entire chromosomes (aneuploidy) or chromosomal segments as a low- cost, high- throughput alternative method to CMA. This is not used in the United States for prenatal diagnosis but is the method of choice for preimplantation genetic testing for aneuploidy.

اخر الاخبار

اخبار العتبة العباسية المقدسة

جناح العتبة العباسية المقدسة في معرض طهران الدولي يشهد فعاليات متنوِّعة

شعبة مدارس الكفيل تطلق حملتها السنوية لدعم العوائل المتعففة في شهر رمضان المبارك

بأجواء رمضانية مميزة.. مجموعة مشاتل الكفيل تستقبل العوائل العراقية يوميًا

المجمع العلمي: الختمة القرآنية الرمضانية المركزية المرتلة تشهد تنوعًا في القراءات والمشاركات

المزيد

الآخبار الصحية

دراسة تكشف "السبب الخفي" وراء ترك التمارين الرياضية

كشف التوقيت "المثالي" لتغيير فرشاة الأسنان

بلاستيك في أنسجة بشرية.. دراسة تكشف مفاجأة طبية

دراسة تحذر من الإفراط في ممارسة الرياضة.. كيف يضر دماءك؟

المزيد

الآخبار التكنلوجية

"ديب سيك" تحجب أحدث نماذجها عن شركات الرقائق الأميركية

"سامسونغ" تطلق سلسلة هواتف "غالاكسي إس 26"

حملات سرية ورسائل تشويه.. كيف يتم استغلال "تشات جي بي تي"؟

أثر نفسي غير متوقع للرياضة.. مرتبط بالغضب

المزيد

مواضيع ذات صلة

Introduction to Cytogenetics and Genome Analysis

The Origin and Frequency of Different Types of Mutation

Noninvasive Prenatal Screening by Analysis of Cell- Free Fetal DNA

Screening for Down Syndrome and Other Aneuploidies

Screening for Neural Tube Defects

Genetic Alterations Associated with Acromegaly

The Profession of Genetic Counseling

Applying Genomics to Individualize Cancer Therapy

The Role of Epigenetics in Cancer

Screening for Genetic Susceptibility to Disease

Pharmacogenomics

Monogenic Diseases Show One of Three Patterns of Inheritance