Juvenile polyposis syndrome (JPS) is an autosomal dominant disorder caused by mutations in the SMAD4 and BMPR1A genes. Juvenile polyps are hamartomatous lesions in the gastrointestinal (GI) tract with a distinct histological appearance of normal epithlium with cystic glands embedded in hyperplastic stroma and inflammatory infiltrate. Juvenile polyps are typically benign, but in individuals with juvenile polyposis syndrome (JPS), there is risk for malignant transformation. Sequence and deletion/duplication analysis of the SMAD4 and BMPR1A genes, as offered at GeneDx, will identify a mutation in approximately 50% of individuals with a clinical diagnosis of JPS.

GeneDx is pleased to announce a first-of-its-kind test that will enable physicians and patients to more accurately identify the genetic cause of rare diseases. This genetic test is useful when a patient has gone through all the routine diagnostic tests and does not yet have a molecular genetic diagnosis.  Based on the test results, physicians will be able to make a specific diagnosis, provide the patient with a specific disease surveillance, prevention, and management. Details…

As of October 3 2011, GeneDx’s Noonan syndrome panel will also include the CBL and NRAS genes. The GeneDx Comprehensive Noonan Syndrome Panel has been expanded to include 11 genes (BRAF, KRAS, HRAS, NRAS, MAP2K1, MAP2K2, PTPN11, RAF1, CBL, SOS1, SHOC2) for post-natal testing. Disorders of the Noonan Spectrum, including Noonan, LEOPARD, Cardio-facio-cutaneous (CFC) and Costello syndromes, are a genetically heterogeneous group of autosomal dominant disorders that often have overlapping clinical features. These disorders result from mutations impacting the Ras/MAPK signaling pathway.

The GeneDx Prenatal Targeted Array is a combined CGH and SNP array for detecting copy number changes and uniparental disomy (UPD), respectively. This array contains 42,000 oligonucleotide probes placed throughout the genome and within 100 common or novel microdeletion and microduplication syndromes as well as those involving subtelomeric regions and any other intrachromosomal region greater than 1.5 Mb. In addition, this array contains 18,000 SNP probes covering chromosomes know to contain imprinted genes (chromosomes 6, 7, 11, 14, 15, 20 and X) and can provide information about the parental origin of chromosomal material. Exon-level probe coverage is added to some genes associated with Mendelian disorders that are detectable prenatally.

Cerebral cavernous malformation (CCM) is a heterogenous disorder that arises from malformed capillary clusters within the central nervous system. Without support of the surrounding brain parenchyma and weakened epithelial walls, blood vessels are prone to leakage. Clinical symptoms range from non-specific headaches to seizures and cerebral hemorrhaging. Diagnostic testing of the three known genes (KRIT1, CCM2, PDCD10) identifies a mutation in ~78% of patients with a family history of CCM. Sequence and deletion/duplication analysis of the KRIT1, CCM2, and PDCD10 genes is available and can be ordered in a tiered manner. 

Visit GeneDx's Booth Exhibit at the American Society of Human Genetics 60th Annual Meeting on November 2-6, 2010 at Washington, DC.


Sessions

Swaroop Aradhya et al. Session 56: Friday, Nov 5th, 1:30pm
Novel pathogenic mutations identified in Mendelian disorders by exon-level array CGH in 3000 clinical cases.

Posters

GeneDx now offers full sequencing and deletion/duplication testing of two additional genes associated with overgrowth syndromes:

1. NSD1  testing for Sotos syndrome
2. GPC3  testing for Simpson-Golabi-Behmel syndrome

The addition of these two new genes expands our growing test menu for genetic disorders associated with pre- and postnatal overgrowth.  GeneDx also offers testing for mutations in the PTCH gene associated with Gorlin syndrome and for PTEN-related disorders, including Bannayan-Riley-Ruvalcaba syndrome and macrocephaly/autism spectrum disorders.

Ectodermal dysplasias are a clinically and genetically very heterogeneous group of disorders. In addition to EDA1 and EDAR testing, GeneDx now offers a diagnostic test for WNT10A-related ectodermal dysplasia. Individuals with WNT10A mutations usually have oligodontia, nail dystrophy, dry skin, excessive or reduced sweating and sparse hair. According to recent studies, mutations in the WNT10A gene have been identified in 9% of patients with ectodermal dysplasia and in as many as 25% of individuals who tested negative for a mutation in the EDA1 gene. Once a mutation in WNT10A has been detected in a proband, carrier testing of relatives and prenatal diagnosis are also available.

GeneDx is the first laboratory to offer testing for deletions/duplications in 10 genes associated with Long QT Syndrome (LQTS). It has been shown that approximately 10% of patients with LQTS who test negative for a mutation by DNA sequencing will have a deletion/duplication that involves one of the LQTS genes (Eddy et al. Heart Rhythm 5:1275-1281, 2008). As such deletions/duplications cannot be detected by either NextGeneration or capillary (Sanger) sequencing, GeneDx has developed a high-resolution oligonucleotide microarray for comparative genomic hybridization (array CGH) with probes concentrated in the exons of 10 LQTS genes.

GeneDx now offers full sequencing of four additional genes associated with disorders of sexual differentiation: