Reproductive genetic counseling challenges associated with diagnostic exome sequencing in a large academic private reproductive genetic counseling practice

Westerfield, Lauren; Stover, Samantha; Mathur, Veena S.; Nassef, Salma; Carter, Tiffiney G.; Yang, Yaping; Eng, Christine M.; Veyver, Ignatia B. Van den

doi:10.1002/pd.4674

Cited by 51 publications

(65 citation statements)

References 20 publications

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“…These guidelines incorporate five categories of variant classification: benign, likely benign, uncertain (variants of uncertain significance (VUS)), likely pathogenic, and pathogenic. 10 An uncertain finding can be frustrating for clinicians and patients, 11 but it is a necessary result when there is insufficient information to determine whether a variant is benign or pathogenic. Reports with uncertain findings can result in additional medical costs and a continued diagnostic odyssey when a provider lacks sufficient information to rule in or rule out a diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Variants of uncertain significance in newborn screening disorders: implications for large-scale genomic sequencing

Narravula

Garber

Askree

et al. 2017

Genetics in Medicine

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Section: Introductionmentioning

confidence: 99%

Variants of uncertain significance in newborn screening disorders: implications for large-scale genomic sequencing

Narravula

Garber

Askree

et al. 2017

Genetics in Medicine

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“…Several studies have shown the clinical utility of DES for prenatal and neonatal patients due to increasing ease of DES and knowledge of the human genome [13–15]. …”

Section: Introductionmentioning

confidence: 99%

Clinical diagnostic exome evaluation for an infant with a lethal disorder: genetic diagnosis of TARP syndrome and expansion of the phenotype in a patient with a newly reported RBM10 alteration

et al. 2017

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BackgroundDiagnostic Exome Sequencing (DES) has been shown to be an effective tool for diagnosis individuals with suspected genetic conditions.Case PresentationWe report a male infant born with multiple anomalies including bilateral dysplastic kidneys, cleft palate, bilateral talipes, and bilateral absence of thumbs and first toes. Prenatal testing including chromosome analysis and microarray did not identify a cause for the multiple congenital anomalies. Postnatal diagnostic exome studies (DES) were utilized to find a molecular diagnosis for the patient.Exome sequencing of the proband, mother, and father showed a previously unreported maternally inherited RNA binding motif protein 10 (RBM10) c.1352_1353delAG (p.E451Vfs*66) alteration. Mutations in RBM10 are associated with TARP syndrome, an X-linked recessive disorder originally described with cardinal features of talipes equinovarus, atrial septal defect, Robin sequence, and persistent left superior vena cava.ConclusionDES established a molecular genetic diagnosis of TARP syndrome for a neonatal patient with a poor prognosis in whom traditional testing methods were uninformative and allowed for efficient diagnosis and future reproductive options for the parents. Other reported cases of TARP syndrome demonstrate significant variability in clinical phenotype. The reported features in this infant including multiple hemivertebrae, imperforate anus, aplasia of thumbs and first toes have not been reported in previous patients, thus expanding the clinical phenotype for this rare disorder.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-017-0426-3) contains supplementary material, which is available to authorized users.

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“…More recently, Alamillo et al reported relevant mutations in four of seven prenatal cases 135 , and Drury et al found a 25% total detection rate in 24 fetuses with abnormal ultrasound findings, including a definitive diagnosis in five and plausible diagnosis in one 11 . Our early results also indicate that the detection rate of a significant genetic abnormality with prenatal exome sequencing for fetuses with single or multiple congenital anomalies is at least 30% 18, 128 .…”

Section: Prenatal Whole-exome Sequencing Will Change Our Ability To Imentioning

confidence: 57%

“…Healthcare providers must consider the consequences of their rapid introduction into the clinic because of the still-limited knowledge about the test performance of some assays in routine clinical practice, concerns related to cost-conscious implementation of optimized screening and testing strategies, equal access, and appropriate selection of who will benefit most. The ever-increasing amount of genetic information that can be obtained preconceptionally and prenatally also brings about ethical and genetic counseling challenges 9, 18– 21 .…”

Section: Introductionmentioning

confidence: 99%

Recent advances in prenatal genetic screening and testing

Veyver

2016

F1000Res

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The introduction of new technologies has dramatically changed the current practice of prenatal screening and testing for genetic abnormalities in the fetus. Expanded carrier screening panels and non-invasive cell-free fetal DNA-based screening for aneuploidy and single-gene disorders, and more recently for subchromosomal abnormalities, have been introduced into prenatal care. More recently introduced technologies such as chromosomal microarray analysis and whole-exome sequencing can diagnose more genetic conditions on samples obtained through amniocentesis or chorionic villus sampling, including many disorders that cannot be screened for non-invasively. All of these options have benefits and limitations, and genetic counseling has become increasingly complex for providers who are responsible for guiding patients in their decisions about screening and testing before and during pregnancy.

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Reproductive genetic counseling challenges associated with diagnostic exome sequencing in a large academic private reproductive genetic counseling practice

Cited by 51 publications

References 20 publications

Variants of uncertain significance in newborn screening disorders: implications for large-scale genomic sequencing

Variants of uncertain significance in newborn screening disorders: implications for large-scale genomic sequencing

Clinical diagnostic exome evaluation for an infant with a lethal disorder: genetic diagnosis of TARP syndrome and expansion of the phenotype in a patient with a newly reported RBM10 alteration

Recent advances in prenatal genetic screening and testing

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