CGC Genetics, a clinical genetics testing company, recently introduced a panel for skeletal dysplasias.
The assay runs on Illumina's digital microbead-based BeadXpress system, and bolsters the Porto, Portugal-based company's menu of Array CGC tests.
Luis Dias, a scientist in CGC's R&D unit, told BioArray News this week that most contemporary tests screen for a specific dysplasia by conducting a complete sequence analysis of the gene.
"This approach can be time consuming and [produce] results [that are] difficult to interpret," Dias said. "Our panel only includes mutations with clear clinical meaning," he claimed.
CGC's panel covers 47 SNP mutations in the six genes associated with different dysplasias — FGFR3, COL2A1, SLC26A2, CRTAP, LEPRE1 and SOX9. A study carried out by CGC with collaborators at Centro Hospitalar do Alto Ave in Guimarães, Portugal, and the department of gynecology and obstetrics at Hospital São Teotónio in Viseu, Portugal, was published last month in the journal Ultrasound in Obstetrics and Gynecology.
In that paper, the authors described the use of CGC's panel to successfully diagnose thanatophoric dysplasia in two prenatal cases. According to the US National Institutes of Health, thanatophoric dysplasia is a severe skeletal disorder characterized by extremely short limbs and folds of extra skin on the arms and legs, and occurs in 1 in every 20,000 to 50,000 newborns.
The authors wrote in the paper that current molecular diagnosis of thanatophoric dysplasia entails testing a large number of genes, one at a time, whereas CGC's "more efficient" approach enables the parallel evaluation of most frequent SD-associated genes and mutations on a customized multiplex panel.
Dias said that CGC chose to include mutations assocuated with the most frequent dysplasias, narrowing in on genes with frequent mutations. "At the end we developed a panel that includes some of the most frequent and also the most lethal forms of SD," he said, though he acknowledged that dominant forms of osteogenesis imperfecta had to be left out "because of the very short number of non-private mutations."
Since introducing its test for skeletal dysplasias, Dias said that CGC has seen "increased demand" for the panel.
"Obstetricians are very prone to request this type of molecular genetic testing since it allows early molecular diagnosis, with clear implications in prenatal care and in counseling for future pregnancies," said Dias. He said that the firm has submitted a new paper for publication that describes the identification of 13 positives in 51 cases of suspected dysplasias.
"The large majority of these cases would remain without a definitive molecular diagnosis if the mutation panel did not exist," claimed Dias.
But CGC is not the only firm to offer a multiplex mutation detection approach for prenatal skeletal dysplasia testing. Northwestern Reproductive Genetics, for instance, offers dysplasia testing using arrayed primer extension panels made by Tartu, Estonia-based Asper Biotech. And Allentown, Pa.-based CTGT offers similar testing on its Agilent Technologies-manufactured HDT Array, albeit on a gene-by-gene basis.
Dias said that CGC chose to use Illumina's BeadXpress over other platforms because it wanted to develop mutation panels grouped by signs and symptoms.
"We began designing our mutation panels based on clinical features of the diseases or disorders, [such as] groups of signs and symptoms," said Dias. This allowed CGC to offer ts BeadXpress-based tests as a first-tier approach, as it could offer a quick diagnosis for patients carrying common mutations.
CGC rolled out its first of such tests in 2009 (BAN 12/21/2010). It currently offers panels for Bardet-Biedl syndrome; congenital deafness, craniosynostosis; Fraser syndrome; metabolic disorders; Noonan and other genetically related syndromes; thrombophilia and warfarin pharmacogenetics; gastrointestinal disorders; and, of course, skeletal dysplasias. Dias added that the firm plans to introduce panels for diabetes and obesity, but did not elaborate.
While Dias said that demand for CGC's tests "could be higher" he said that it has been "increasing consistently." He added that the firm hopes that research papers and case reports on its Array CGCs will "help the medical community see the benefits of this approach."