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News Archive


December, 2006

SOS1 gene analysis is here! GeneDx announces expanded, comprehensive, cost-saving testing strategies for Noonan syndrome.

Approximately 61% of individuals with a clinical diagnosis of Noonan syndrome (NS) are expected to have a mutation in 1 of 3 functionally related genes, PTPN11, SOS1, and KRAS.

Germline mutations in the SOS1 gene account for NS in about 10% of all patients, and in 20% of those who do not have a mutation in the PTPN11 gene.

GeneDx now offers two testing strategies for molecular diagnosis of Noonan syndrome: Sequential tiered testing is the most cost-effective approach for your patient, and is predicted to identify 94% of existing NS-associated mutations for a cost of $1800 (levels 1-3). Our Comprehensive Noonan syndrome panel is more time-efficient, providing simultaneous testing of the PTPN11, SOS1, and KRAS genes for significantly shorter turn-around-times. This panel is predicted to detect >99% of existing mutations in these three genes. Alternatively, testing for PTPN11, SOS1, and KRAS can be ordered individually.

Kallmann Syndrome testing (KAL1, FGFR1) now available as part of the CETT initiative

GeneDx announces the addition of genetic testing for Kallmann syndrome, characterized by idiopathic hypogonadotropic hypogonadism (IHH) and a defective sense of smell (hyposmia/anosmia). This disorder is genetically heterogeneous and more than 4 different genes have been identified already. Five to eight percent of patients with Kallmann syndrome are expected to have a mutation in the X-linked KAL1 gene that can be detected by DNA sequencing, and eight to sixteen percent are expected to have a mutation in the autosomal FGFR1 gene. The overall test sensitivity is approximately 25%. Analysis of the KAL1 gene is warranted in all males with Kallmann syndrome (IHH and anosmia/hyposmia). If negative for a KAL1 mutation, FGFR1 analysis is recommended. Analysis of FGFR1 is warranted in all females with Kallmann syndrome and all males and females with IHH and a normal sense of smell.

Testing for KAL1 and FGFR1 in Kallmann syndrome is offered as part of the "Collaboration, Education and Test Translation (CETT) Program" developed by the NIH Office of Rare Diseases with the ultimate goal to collect both clinical and molecular data and develop improved and essential genotype-phenotype correlations. Completion of the Kallmann syndrome clinical data sheet for each patient tested is a necessary step towards this goal. We appreciate your assistance.

November, 2006

GeneDx announces a new test for detecting the common filaggrin gene (FLG) mutations R501X and c.2282del4, which account for 80%-90% of cases with Ichthyosis Vulgaris in the Northern and Western European and White US population. In addition to Ichthyosis Vulgaris, both mutations are also considered to be major predisposing factors for atopic dermatitis (AD) and AD-associated asthma and allergic rhinitis.

October, 2006

GeneDx, Inc. expands the test menu for developmental eye disorders and glaucoma.

We have launched genetic testing for Axenfeld-Rieger syndrome (ARS), a spectrum of disorders of the anterior segment of the eye, including Axenfeld anomaly, Rieger anomaly, Rieger syndrome, iridogoniodysgenesis, iris hypoplasia and Peter’s anomaly. About half of affected patients with ARS are expected to develop glaucoma in their lifetime. Extra-ocular findings, such as dental hypoplasia, craniofacial dysmorphism, and redundant umbilical skin, cardiac defects, limb anomalies, pituitary abnormalities, and sensory hearing loss are present in some cases. ARS is inherited in an autosomal dominant pattern, although sporadic cases are not uncommon.

Mutation analysis is now available for PITX2 and FOXC1, the two most common genes associated with ARS. In general, mutations in the PITX2 gene are seen more frequently in patients with ocular and systemic anomalies, whereas mutations in FOXC1 are found in patients with isolated ocular findings.

The addition of PITX2 and FOXC1 considerably expands our ophthalmological test panel that also includes anophthalmia and microphthalmia with or without coloboma (SIX6, SOX2, and PAX6 genes), aniridia, optic nerve hypoplasia and anomalies and corneal dystrophy (PAX6 gene), X-linked retinoschisis (RS1 gene), CHARGE syndrome (CHD7 gene) and Hermansky-Pudlak syndrome (HPS1 and HPS3 genes).

GeneDx announces two new tests for congenital genetic disorders: Cohen syndrome and Townes-Brocks syndrome.

COH1 gene analysis in Cohen syndrome
Cohen syndrome is characterized by hypotonia, failure to thrive and delayed psychomotor development, microcephaly, obesity, eye abnormalities, neutropenia and characteristic facial features. This autosomal recessive disorder is overrepresented in the Finnish and Amish populations but has been reported world-wide. The significant phenotypic variability among non-Finnish patients with Cohen syndrome may pose diagnostic difficulties. Hence Cohen syndrome is often considered in the differential diagnosis of the following syndromes:
  • Prader-Willi and Angelman syndromes in patients with normal DNA methylation studies
  • Williams syndrome in patients without a detectable microdeletion
  • Bardet-Biedl syndrome.
Mutation analysis of the COH1 gene will be helpful in establishing the diagnosis of Cohen syndrome, for prenatal diagnosis in at-risk pregnancies, carrier testing of family members and genetic counseling.

SALL1 gene analysis in Townes-Brocks syndrome (TBS)
Townes-Brocks syndrome is an autosomal dominant multiple malformation disorder with anorectal abnormalities, anomalies of hands and feet, external ear malformations, hearing loss, and renal abnormalities leading to impaired renal function or renal failure. The clinical features of TBS overlap with VATER and VACTERL associations, oculo-auriculo-vertebral (OAV) spectrum, branchio-oto-renal (BOR) syndrome, and Fanconi anemia and other 'anus-hand-ear' syndromes.

Testing for SALL1 gene mutations in TBS expands our menu for hereditary limb defects and hereditary eye disorders, such as Holt-Oram syndrome, Hereditary Multiple Exostoses, Cartilage Hair Hypoplasia, Ectrodactyly-Ectodermal Dysplasia-Clefting Syndrome, Limb-Mammary Syndrome, Multiple epiphyseal dysplasia, and Charge syndrome.

June, 2006

Gene analysis for Cardio-Facio-Cutaneous (CFC) Syndrome, Costello Syndrome, and Noonan syndrome:

We offer a cost effective, two-tiered testing approach for bidirectional sequence analysis of the BRAF gene in CFC and of the HRAS gene in Costello syndrome, in addition to a more efficient and cost-effective protocol for PTPN11 analysis in Noonan and LEOPARD syndrome. In addition, KRAS testing is available for patients with Noonan or CFC syndrome.

In CFC syndrome, mutation analysis of the BRAF and KRAS genes is available. Recent studies estimate that between 40% and 70% of affected individuals will have mutations in the BRAF gene, while about 7% will have a mutation in the KRAS gene. BRAF analysis, Tier 1 includes bidirectional sequencing of 5 selected exons (exons 6, 11, 12, 14, and 15), where all mutations have been found to date. Sequencing of the remainder of the gene (Tier 2 analysis) is available if necessary. KRAS testing encompasses sequence analysis of the entire coding region (exons 2-6).

In Costello syndrome, 82%-92% of patients are expected to have a mutation in the HRAS gene. Our initial analysis includes bidirectional sequencing of exon 2 of the HRAS gene, where almost all mutations have been found to date. If no mutation is detected, the remaining coding exons of the HRAS gene (exons 3 to 6) are analyzed.

Noonan syndrome is genetically heterogeneous. The overall mutation rate in the PTPN11 gene is 50% (familial and sporadic cases), while about 2% of patients without PTPN11 mutation are expected to have a KRAS mutation. In Noonan syndrome, exons 3, 8, 9, and 13 are sequenced in the Tier 1 analysis. In LEOPARD syndrome, Tier 1 analysis includes sequencing of exons 7, 12 and 13. If no mutation is found, the remaining PTPN11 exons are screened by bi-directional sequence analysis in Tier 2. Using this two-tiered approach, we expect to identify over three-quarters of PTPN11 mutations in the first testing tier, thereby keeping the cost down for the majority of patients. KRAS testing encompasses sequence analysis of the entire coding region (exons 2-6).

GeneDx offers testing for Niemann-Pick Disease, Type C (NPC)

Niemann-Pick Disease, Type C (NPC) is a rare and sometimes fatal lipid storage disorder. Bidirectional sequence analysis is now available for the NPC1 and NPC2/HE1 genes associated with Niemann-Pick Disease, Type C. As approximately 90% of patients with NPC will have mutations in NPC1, testing for this gene is recommended before testing of NPC2/HE1. The overall sensitivity for the combined testing (NPC1 and NPC2 genes) approaches 94%. Carrier testing and prenatal diagnosis for NPC is available if the mutation(s) in a family have been identified.

May, 2006

New Service:

CopyDxSM - Deletion/Duplication Analysis for any X-Linked Disorder and a growing list of autosomal disorders due to haploinsufficiency. CHARGE syndrome (CHD7), Alagille syndrome (JAG1), Smith-Magenis syndrome (RAI1), Multiple Endocrine Neoplasia/Familial Medullary Thyroid Carcinoma (RET), and Developmental eye disorders including microphthalmia and anophthalmia (SOX2) are available NOW. More autosomal genes to come!

A landmark service for the diagnosis of whole and partial gene deletions or duplications based on the innovative use of quantitative PCR-technology to determine the copy number of genes using genomic DNA from patients. High resolution analysis is achieved by probing very short genomic sequence segments (~100 bp) and determining whether one or several copies are present in the genome.

Clinical applications include:
  • Diagnosis of a deletion syndrome, complementing or replacing FISH analysis.
  • Carrier testing for at-risk relatives (particularly at-risk female carriers of males with multiexonic or whole gene deletions).
  • Evaluation for the presence/absence of a specific gene within a contiguous gene deletion syndrome.

Meet our new genetic counselors:


Heather Ferguson, M.S., C.G.C.

Allison G. Mitchell, M.S., C.G.C.

Brandi L. Blaisdell

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