Same-Day Fluorescence In Situ Hybridization (FISH)

FISH genetic testing is used to quickly detect many of the most common chromosome abnormalities, such as:

• Down syndrome

• Trisomy 18

• Trisomy 13

• Sex chromosome abnormalities

When the CVS or amniocentesis sample is received by the laboratory in the morning, IMG can provide same-day FISH results.

Karyotyping

A full chromosome analysis, called a karyotype, is the standard for prenatal diagnosis of chromosome abnormalities, following a CVS or amniocentesis procedure.

Depending on the extent to which the cells need to be grown in culture, it can take up to two business weeks to see results. Insight Medical Genetics will contact providers as soon as the final karyotype is complete.

Chromosome Microarray Analysis

Insight Medical Genetics can also test a CVS or amniocentesis specimen using prenatal chromosome microarray (CMA) analysis. The American Congress of Obstetricians and Gynecologists and the Society for Maternal Fetal Medicine recommend CMA for prenatal diagnosis as the test that can detect the small chromosome abnormalities conventional karyotyping cannot identify.

The IMG microarray panel targets approximately 80 known genetic syndromes associated with microdeletion and microduplication syndromes that may cause birth defects and developmental or intellectual disabilities. The CMA will also evaluate for other deletions, duplications and abnormalities above a 1 Mb threshold.

IMG will perform chromosomal microarray analysis on a specimen obtained by diagnostic procedure following an abnormal ultrasound and/or negative FISH result.

A five-cell karyotype also accompanies all microarray analyses to identify translocations or mosaicism that may be present.

Send-In Specimen for Chromosomal Microarray Analysis

Certain DNA extraction methods may affect the quality of microarray test results. IMG recommends sending either of the following samples:

• Direct chorionic villi: 15-20mg

• Direct or cultured amniotic fluid: 2 T-25 flasks of confluent fetal cells

A maternal blood sample is also required to conduct the necessary maternal cell contamination studies prior to all prenatal CMA tests.

POC ANALYSIS: We welcome product of conception (POC) specimens and will perform a combination of karyotype and chromosomal microarray analysis. Please contact us for details, specimen requirements, and turnaround times to meet your needs. 

Noonan Syndrome Panel

IMG offers a next-generation exome sequencing panel for Noonan and Noonan-related syndromes, autosomal dominant conditions characterized by short stature, congenital heart defect and developmental delay. IMG tests for mutations in 11 genes associated with Noonan and Noonan-related syndromes: PTPN11, KRAS, SOS1, RAF1, BRAF, CBL, NRAS, HRAS, SHOC2, MAP2K1, and MAP2K2. The custom designed assay covers over 98% of the coding bases and +/- 30bp of sequences flanking each exon; the assay has a sensitivity of 99.1% and specificity of 99.99%.

Noonan syndrome prenatal genetic testing is recommended for fetuses with increased nuchal translucency and normal karyotype. All positive findings are confirmed by Sanger sequencing.

Skeletal Dysplasia Panel

IMG provides prenatal patients with early genetic testing for mutations associated with skeletal dysplasia. 

• The Skeletal Dysplasia Testing Panel is usually applied to abnormal skeletal findings on ultrasound examination and may also be appropriate for fetuses with increased nuchal translucency and normal karyotype along with the Noonan syndrome panel. 
• The panel uses next-generation sequencing with Sanger confirmation to test for 464 known mutations in eight genes associated with prenatal or perinatal onset skeletal dysplasias. Previously unreported findings are analyzed using different combinations of prediction software. 
• The table below summarizes the mutations covered in the Skeletal Dysplasia panel:

Osteogenesis Imperfecta Panel

IMG offers an exome sequencing panel that tests for osteogenesis imperfecta (OI), a genetic condition characterized by susceptibility to bone fractures with a range of severity. OI can derive from multiple genes and IMG offers genetic testing that covers more than 99% of the coding regions of 14 targeted genes. At least 15 base pairs on either side of each exon are also sequenced for 201 of the 205 targeted exons (approximately 97%). A majority of the targets are sequenced by next-generation parallel sequencing, while a small number require sequencing using the Sanger method. Sanger sequencing confirms all disease-associated variants detected using the next-gen approach. The analytic sensitivity and specificity of the assay are both greater than 99%. 

IMG recommends OI testing in conjunction with the Skeletal Dysplasia panel when ultrasound findings are unable to differentiate between the two conditions. 

The clinically and radiologically differentiated types of OI have undergone multiple classification schema, due in large part to the recognition of a growing number of non-COL1A1 or COL1A2 causative genes. The table below lists the 14 genes in IMG’s OI panel along with the associated OI types, modes of inheritance, and any related disorders with known mutations in each genes.

Fragile X Syndrome

Fragile X syndrome is associated with the FMR1 gene and is the most common form of inherited intellectual disability.  Fragile X testing is used to determine the number of CGG trinucleotide repeats, an unstable genetic sequence that expands from one generation to the next.

The analysis of the FMR1 gene at IMG includes both an assessment of the CGG repeat number and the methylation status of the promoter, the latter of particular importance for a complete evaluation when a full mutation is detected.

FMR1 mutations are associated with fragile X syndrome, fragile X tremor/ataxia syndrome (FXTAS), and premature ovarian failure (FXPOI). The results of an FMR1 analysis are divided into four categories: normal range (6-44 repeats), intermediate zone (45-54 repeats), premutation (55-200 repeats),  and full mutation (>200 repeats).

IMG will perform fragile X testing on prenatal samples as well as blood specimens from adults.

Spinal Muscular Atrophy Testing

Spinal muscular atrophy (SMA) is a progressive neurologic condition primarily associated with the SMN1 gene. SMA can lead to an early infant death, though some children won’t show signs of the disease for several years.

The vast majority of people who are affected with SMA have a deletion in both copies of the SMN1 gene that leads to a non-functioning protein.  This accounts for ~95% of cases of SMA.  There are also instances of point mutations that contribute to the incidence of SMA, and taken together with the deletion-based cause account for 98-99% of SMA cases.  The remaining 1-2% are due to an unusual configuration of the SMN1 gene.

SMA is inherited as an autosomal recessive condition, which means that only when both parents are carriers, there is a 25 percent chance of their child being born with SMA. Because of the frequency of SMA, approximately 1 in 40-65 depending on the ethnic background of the population and the ability to test for carriers of an altered SMN1 gene, the American College of Medical Genetics recommends that all prospective parents be screened.  

IMG offers both deletion testing and point mutation screening for adults as well as prenatal testing for carrier couple parents.

Complete Gene Sequencing by Sanger Technology

Partner Reflex Sequencing

Other Molecular Testing

Coming Soon...

IMG offers complete gene sequencing by Sanger technology (coding exons +/- 30 bp of flanking intron) for the following, continually expanding list of genes/conditions:

• ACADS  – Short chain acyl-CoA dehydrogenase deficiency
• ALDOB – Hereditary fructose intolerance
• ASPA – Aspartoacylase deficiency/Canavan disease
• CFTR – Cystic Fibrosis
• CPT2 – Carnitine palmitoyltransferase II deficiency
• DHCR7 – Smith-Lemli-Opitz syndrome
• G6PC – Glycogen storage disease type 1a
• GAA – Glycogen storage disease type II/Pompe disease
• GBA – Gaucher Disease – IMG uses a combination of the long-range PCR and Sanger sequencing to assess the complete GBA gene while distinguishing it from a non-functioning but related pseudogene.
• GJB2- GJB2-related DFNB1 nonsydromic hearing loss
• HEX A – Tay-Sachs disease
• MEFV – Familial Mediterranean fever
• PMM2 – Hereditary disorder of glycosylation type 1a

Insight Medical Genetics offers rapid turnaround times for the reflex Sanger sequencing of the most commonly found recessive genes on many extended genotyping panels. Reflex sequencing is the best and most complete clinical strategy for assessing the risk of a couple giving birth to a child affected with the tested condition.  

Reflex sequencing should be performed on the spouse/partner of an individual who has already been determined to be a carrier of a mutation in one or more genes by prior genotype screening.  For example, if a woman who is currently pregnant or is planning to become pregnant is identified as a carrier by a genotyping panel, it is better to pursue full gene sequencing for the spouse or partner, which will yield a more complete assessment of his mutation status for that gene; reflexing to a genotyping panel would only test for the most common mutation, leaving considerable residual risk.

IMG will provide reflex sequencing within seven business days of specimen receipt for the above list of genes. As our capabilities continue to grow, please contact us for a complete list of genes.

Custom designed gene sequencing may also be developed on a case-by-case basis. Please contact us for details.

• GJB2/GJB6 deletion testing – DFNB1 non-syndromic hearing loss
• COL1A1/COL1A2 deletion testing – Osteogenesis Imperfecta

• HBA deletion testing – Alpha thalassemia
• HBA1/HBA2 Sanger Sequencing – Alpha thalassemia
• HBB Sanger Sequencing – Beta thalassemia, sickle cell disease, hemoglobin C disease, Hemoglobin E disease