Whole exome sequencing in inherited endocrine disorders

Division of Human Genetics Diagnostic Laboratories

To date, the U. However, even among the 56 genes recommended for the reporting of incidental findings by the ACMG, there are challenges in determining phenotype consequences of variants identified. Patients who have multiple congenital anomalies or a neurodevelopment disorder with a suspected genetic etiology, but the specific alteration is unclear or unidentified by a standard clinical workup chromosomal microarray analysis, chromosomal karyotype, fluorescence in situ hybridization FISHmetabolic testing, imaging, single gene tests, referrals to other specialistsmay be left without a clinical diagnosis of their disorder, despite a lengthy clinical workup.

Informed consent was obtained from all parents or guardians. Clinical Utility A genetic diagnosis for an unexplained disorder can alter management in several ways: Genetic Counseling Experts recommend formal genetic counseling for patients who are at risk for inherited disorders and who wish to undergo genetic testing.

Individuals should not be employed by a commercial genetic testing laboratory unless they are employed by or contracted with a laboratory that is part of an integral Health System which routinely delivers health care services beyond just the laboratory test itself.

While incidental identification of clinically significant mutations pose issues of informed consent, these findings often have medical management recommendations.

Data Analysis The laboratory implements dual bioinformatics analyses pipelines that include the use of NextGene V2. For example, information regarding whether a candidate variant is de novo or inherited provides powerful evidence of its potential pathogenicity, thereby giving the finding utility in other family members.

The phenotype or family history data strongly implicates a genetic etiology, but the phenotype does not correspond with a specific disorder for which a genetic test targeting a specific gene is available on a clinical basis. This clinical utility is independent of whether the affected family member has benefited directly from this diagnosis.

These rates can be expected to be significantly higher than seen when array comparative genomic hybridization is used in prenatal diagnosis.

Some studies reported on the use of a virtual gene panel with restricted analysis of disease-associated genes, and the authors noted that WES data allows reanalysis as new genes are linked to the patient phenotype.

In family 1 the proband family 1: Genetic Counseling Due to the likelihood of the discovery of a variant of uncertain significance or other incidental findings, pre-and-post genetic counseling for any individual undergoing WES is required.

Representing IGV view of the mutation rs in the patient sample. It is generally considered to be divided into two categories. Exome analyses interrogate thousands of genetic variants in a proband and a subset of these is identified as potentially clinically relevant.

Early use of WES can reduce the time to diagnosis and reduce the financial and psychological burdens associated with prolonged investigation. Given the variety of disorders and management approaches, there are a variety of potential health outcomes from a definitive diagnosis.

WGS has greater ability to detect large deletions or duplications in protein-coding regions compared with WES, but requires greater data analytics. WES has also been reported to be beneficial in patients with atypical presentations. Based on the peer reviewed medical literature the evidence is insufficient in proving the clinical utility of this technology in the use of prenatal and preimplantation genetics.

Clinical symptoms of affected patients are decreased vision, night blindness, visual field constriction and progressive vision loss between third and fourth decade of life.

This is an Open access article distributed under the terms of Creative Commons Attribution 4. Some studies used a virtual gene panel that is restricted to genes that are associated with the phenotype, while others have examined the whole exome, either initially or sequentially.

The largest reason for referral to a tertiary care center was an unexplained neurodevelopmental disorder. Comparators The relevant comparator of interest is standard clinical workup without WES.

In view of the long turnaround times and interpretive complexities currently associated with this technology, preconception carrier screening is strongly favored over post-conception screening.

MP 0102 - Whole Exome and Whole Genome Sequencing for Diagnosis of Genetic Disorders

Another heterozygous pathogenic mutation without any assertion criteria rs in RPGRIP1 gene retinitis pigmentosa GTPase regulator interacting protein 1 was observed to be associated with autosomal recessive Cone-rod dystrophy 13 CORD13loss of central vision, color vision defects, later followed by progressive loss in peripheral vision and night blindness.

WES not only enhances our present understanding of genetic basis of retinal disorders but also provides insight to carry out further investigation for similar cases.Please Enter Your Information to Continue.

First name. Last name. To identify novel genetic causes of rare inherited endocrine disorders in children with a focus on congenital hyperinsulinism, short stature of unknown etiology and IGF1 abnormalities by using whole exome sequencing.

Based on our own recent experiences with exome sequencing in a research context, we describe the general clinical ascertainment of relevant pediatric endocrine patients, compare different formats. Whole Exome and Whole Genome Sequencing for Diagnosis of Genetic Disorders Policy # Original Effective Date: 11/20/ Current Effective Date: 12/20/ Information about whole exome sequencing for healthcare professionals from Cincinnati Children's.

Entire Site; mutations in the exons account for many genetic disorders. Whole exome sequencing (WES) examines the majority of exons and exon / intron boundaries of most of the genes at one time.

This whole exome sequencing test attempts to. Blueprint Genetics offers comprehensive genetic diagnostics for inherited diseases of the endocrine system and infertility.

Whole Exome Sequencing Family Member Testing Many endocrine disorders may present as part of a syndrome with multiple manifestations. Therefore, accurate molecular diagnosis is important for optimizing treatment.

Whole exome sequencing in inherited endocrine disorders
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