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خرید پکیج

تعداد آیتم قابل مشاهده باقیمانده : 3 مورد

Genetic evaluation of the anomalous fetus: Testing options

Genetic evaluation of the anomalous fetus: Testing options

Testing modality	Indications/advantages	Resolution	Limitations
Fluorescence in situ hybridization (FISH)	Rapid and accurate detection of aneuploidies involving chromosomes 13, 18, 21, X, and Y. Can also assess selected deletions and duplications (eg, 22q11.2 [DiGeorge] deletion syndrome).	N/A	Requires follow-up testing with karyotype or microarray. Primarily useful when aneuploidies involving chromosomes 13, 18, 21, X, and Y are suspected.
Karyotype	Used to identify aneuploidies or structural changes, such as balanced and unbalanced translocations, inversions, mosaicism, marker chromosomes, and chromosomal rings. Low level of uncertain results since variants of uncertain significance are not detected.	5 to 10 Mb	Lower resolution than chromosomal microarray and molecular techniques so lower detection rate for clinically significant disorders. Requires cell culture so results are not available for at least 7 days.
Chromosomal microarray analysis (CMA)	Used to detect smaller gains and losses of genetic material than possible with conventional karyotype. Can be performed on uncultured cells (including nonviable cells from stillborns) so rapid turnaround time.	10 to 100 kB	Possibility of identifying incidental findings, variants of unknown significance, consanguinity, or adult-onset diseases. Does not demonstrate genomic location of CNV (cannot distinguish between trisomy 21 versus Robertsonian translocation). Does not detect balanced translocations or inversions. Does not detect regions of homozygosity or triploidy.
Targeted gene sequencing (massively parallel sequencing of specific genes or group of genes known to be associated with a genetic condition)	Used to detect a limited number of monogenic disorders. Most useful when the phenotype is clear, a specific single-gene disorder is suspected, and the gene panel includes most of the relevant genes for possible genetic disorders involving that phenotype.	Single base pair	Targeting the best panel can be challenging. Prenatal assessment of phenotype can be difficult since it is based on imaging, which is affected by gestational age, fetal position, and maternal habitus. Prenatal phenotype may be different from postnatal phenotype. Interpretation of results can be complex. Recommend consultation with genetic counselor or medical geneticist.
Exome sequencing (sequencing of regions of the genome known to encode proteins)	Used to detect monogenic disorders. More comprehensive than a targeted gene panel. Recommended when the fetus has a single major anomaly or multiple organ system anomalies suggestive of a possible genetic etiology, but CMA is not diagnostic or without prior CMA when the fetal phenotype strongly suggests a single-gene disorder. Also recommended in the setting of a previous fetus/child with an anomaly or anomalies suggestive of a genetic etiology but without definitive diagnosis and recurrence of similar anomalies in the current pregnancy.	Single base pair	Exome includes 1% of the genome and 85% of disease-causing mutations. Relevant genes may be missed because of technical issues and because of inability to detect variants in noncoding regions, triplet repeat disorders, small insertions and deletions between 100 and 100,000 base pairs, structural variants (rearrangements and translocations), and some CNVs. Long turnaround time (typically 3 to 4 weeks). Interpretation of results can be complex. Recommend consultation with genetic counselor or medical geneticist.
Whole genome sequencing (nonselective sequencing of coding and noncoding regions of the genome)	Used to detect monogenic disorders. Most comprehensive testing technique (can detect some variants not detectable with exome sequencing). Rapid turnaround time.	Single base pair	Costly. Interpretation of results can be complex. Recommend consultation with genetic counselor or medical geneticist.

N/A: not applicable; Mb: megabase; CMA: chromosomal microarray analysis; kB: kilobase; CNV: copy number variant.

References:

Van den Veyver IB, Chandler N, Wilkins-Haug LE, et al. International Society for Prenatal Diagnosis Updated Position Statement on the use of genome-wide sequencing for prenatal diagnosis. Prenat Diagn 2022; 42:796.
Monaghan KG, Leach NT, Pekarek D, et al. The use of fetal exome sequencing in prenatal diagnosis: a points to consider document of the American College of Medical Genetics and Genomics (ACMG). Genet Med 2020; 22:675.

Courtesy of Neeta Vora, MD, and Sarah Harris, MD, MS.

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