CGC Mutation Panels
MOLECULAR DIAGNOSIS OF THROMBOPHILIA AND WARFARIN PHARMACOGENETICS
Thrombophilia is defined as a predisposition for thrombosis which can arise from genetic factors, acquired changes in the clotting mechanism,
or, more commonly, an interaction between genetic and acquired factors. About 40% of patients with thrombosis have inherited the disease.
The clinical expression of an inherited thrombophilia is influenced by multiple factors such as the number the risk alleles, coexisting genetic or
acquired thrombophilic disorders, and circumstantial risk factors, which have a supra-additive effect on overall thrombotic risk.
Genetic thrombophilia is suspected to account for about 30% of these obstetrical complications. Poor pregnancy outcome is associated with maternal thrombophilia but may also be associated with fetal thrombophilia by inheritance of maternal and paternal thrombophilic genes.
With this panel, we intend to improve the identification of the most relevant factors involved in inherited thrombophilia. It must be
noted that a negative result does not exclude a thrombophilia, because there are other causal factors not included in this panel.
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MOLECULAR DIAGNOSIS OF CRANIOSYNOSTOSIS
Craniosynostosis is a condition characterized by premature closure of calvarial skull bones, caused by the fusion, before the proper time, of one or more cranial sutures (Chun et al., 2003; Cohen, 2005). This results in an abnormal shape of the skull and face. With many sutures closing prematurely, the skull cannot expand to accommodate the growing brain, which leads to several consequences, including developmental delay and mental retardation. Problems with vision and hearing can also appear. The overall incidence for all forms of craniosynostosis is 1:2000-1:2500 live births (French et al., 1990; Lajeunie et al., 1995).
This multiplex mutation test contains a panel of 58 point mutations, identified in 4 main genes involved on syndromic craniosynostosis.
As described in the literature (Chun K et al., 2003), with this set of mutations it is possible to identify the molecular basis of the most frequent and severe forms of genetic craniosynostosis syndromes.
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MOLECULAR DIAGNOSIS OF SKELETAL DYSPLASIA
Osteochondrodysplasias, also known as Bone Dysplasias or Skeletal Dysplasias account for over 450 different genetic diseases with bone involvement but variable clinical characteristics (Superti-Furga and Unger, 2007; Krakow,2008), whose diagnosis is based on clinical examination, radiological findings, histo-pathological and molecular analysis.
SD’s represent approximately 5% of genetic diseases of the newborn (Orioli et al.1986) and cause major problems for families and patients such as morbility, high lethality and complex medical problems, that emerge after the prenatal period. In many cases there is a high risk of recurrence in children or siblings.
Genetic testing can improve the clinical diagnosis and is an important component for a differential diagnosis.
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MOLECULAR DIAGNOSIS OF CONGENITAL DEAFNESS (SYNDROMIC AND NON SYNDROMIC)
Congenital Hearing Loss is the most common birth defect and the most prevalent sensorineural disorder in developed countries (Hilgert et al., 2008). It is estimated that one out of every 500 newborns has bilateral permanent sensorineural hearing loss of ≥ 40 dB; by adolescence, prevalence increases to 1 per 300 (Morton & Nance 2006).
Genetic factors are considered to cause more than 50% of the cases of Congenital Hearing Loss in children. Genetic hearing loss can be inherited, as an autosomal dominant, autosomal recessive, or X-linked recessive trait, as well as by mitochondrial inheritance.
This multiplex mutation test contains a panel of 310 point mutations, identified in the 31 principle genes involved in congenital hearing loss, both Syndromic (175) and Nonsyndromic (135):
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MOLECULAR DIAGNOSIS OF METABOLIC DISEASES
In a broad sense, a metabolic disorder is any disease that is caused by an abnormal biochemical reaction in the body. Most disorders of metabolism involve either abnormal levels or activities of enzymes or hormones, which can lead to serious symptoms or even death if they are not controlled with diet or medication from an early age. There is often a genetic mutation that can be inherited behind the metabolic defect, with an associated risk of recurrence.
Metabolic disorders represent a challenge in diagnosis since they could be present at birth, share a panel of symptoms (like failure to thrive,
neuromotor disabilities, acidosis or ketosis, multi-systemic manifestation), could be lethal or life altering but have different etiology.
Molecular diagnosis has improved and complements the clinical diagnosis at the very early steps of development, allowing prenatal genetic
counseling and early treatment options.
This multiplex mutation test contains a panel of 102 point mutations, identified in the 26 principle genes involved on metabolic inherited disorders, allowing the identification of the molecular basis of the more frequent or severe forms.
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MOLECULAR DIAGNOSIS OF BARDET-BIEDL SYNDROME
Bardet-Biedl Syndrome (BBS) is a pleiotropic ciliopathy characterized by inducing alterations in diverse body systems leading to a wide range of clinical features. Its prevalence is estimated at 1/150,000. Its main features are obesity, progressive pigmentary retinopathy, post-axial polydactyly, polycystic kidneys, hypogenitalism, and learning disabilities. Pigmentary retinopathy is always present in adults. Other frequent
complications include congenital cardiopathy and Hirschsprung disease, diabetes mellitus and hypertension. People with BBS will need multidisciplinary medical care. The renal abnormalities are life-threatening and may lead to renal transplantation. Progressive vision loss, some degree of intellectual deficit and obesity can severely impair the life quality of the affected persons. The differential diagnosis includes Alström, McKusick-Kaufmann, Meckel-Gruber, Joubert, Senior-Loken syndromes and Leber Congenital Amaurosis.
This multiplex mutation test contains a panel of 129 mutations identified in the 13 principle genes involved in Bardet-Biedl syndrome.
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MOLECULAR DIAGNOSIS OF NOONAN SYNDROME AND OTHER GENETICALLY RELATED SYNDROMES
Noonan syndrome is a congenital genetic disease that affects both
males and females equally (1:1.000-2.500 newborns). A great
clinical variability has been identified and the principal features are:
• Heart disease, present in 50-90% of cases, usually valvular pulmonary stenosis or hypertrophic cardiomyopathy
• Short stature of postnatal onset, present in about half of individuals
• Delay of psychomotor development – in about one third of cases adults have mild mental retardation
• Short or webbed neck, pectus excavatum, cryptorchidism, peculiar face
Often this syndrome is not diagnosed, but is related to many complex problems such as coagulation defects and lymphatic dysplasias. The diagnosis enables early treatment, a specific surveillance of the less common complications, and an accurate NOONAN SYNDROME AND OTHER GENETICALLY RELATED SYNDROMES path to genetic counseling. An individual with an identified mutation has a 50% risk of transmitting the syndrome to every one of his descendants, being prenatal molecular diagnosis advised. Affected individuals may have received the mutation from one of the parents (14-75% of cases) or the mutation may have a de novo origin.
This multiplex mutation test contains a panel of 80 point mutations identified in the 8 principle genes involved in Noonan Syndrome and other genetically related syndromes.
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GASTROCHIP
The test is performed using a DNA sample. This can be obtained from peripheral blood, saliva or oral mucosa cells obtained by swab.
The test is performed by microarray hybridization and identifies polymorphisms in genes that encode proteins involved in different gastrointestinal diseases: 15 variants in 9 genes: NOD2 (CARD15), IL23, ATG16L1, IBD5, IL18RAP, MCM6, MYO9B, RGS1 and ALDOB. It also probes alleles HLA DQA1*501, DQB1*201 and HLA-DRB1*04.
Composition of the test:
Food intolerance
• Lactose
• Fructose
• Gluten (Celiac Disease)
Inflammatory Bowel Disease
• Crohn’s Disease
• Ulcerative Colitis
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