Publications by authors named "Slavotinek A"

Purpose: Limited evidence evaluates parents' perceptions of their child's clinical genomic sequencing (GS) results, particularly among individuals from medically underserved groups. Five Clinical Sequencing Evidence-Generating Research (CSER) consortium studies performed GS in children with suspected genetic conditions with high proportions of individuals from underserved groups to address this evidence gap.

Methods: Parents completed surveys of perceived understanding, personal utility, and test-related distress after GS result disclosure.

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  • - Coloboma is a rare congenital condition where part of the eye's tissue is missing, potentially leading to visual impairments; this study analyzed data from the Texas Birth Defects Registry spanning 1999 to 2014 to better understand its prevalence.
  • - The research identified 1,587 coloboma cases, noting that about 58.8% were nonsyndromic, and highlighted key factors affecting prevalence, such as maternal education, race/ethnicity, plurality of births, and maternal diabetes.
  • - The findings suggest a rising trend in coloboma cases over the years and could help target screening efforts for at-risk populations, potentially improving outcomes for future children.
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An increasing number of individuals with intellectual developmental disorder (IDD) and heterozygous variants in BCL11A are identified, yet our knowledge of manifestations and mutational spectrum is lacking. To address this, we performed detailed analysis of 42 individuals with BCL11A-related IDD (BCL11A-IDD, a.k.

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Objective: Occurring once in every 2000 live births, craniosynostosis (CS) is the most frequent cranial birth defect. Although the genetic etiologies of syndromic CS cases are well defined, the genetic cause of most nonsyndromic cases remains unknown.

Methods: The authors analyzed exome or RNA sequencing data from 876 children with nonsyndromic CS, including 291 case-parent trios and 585 additional probands.

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Purpose: Research that includes diverse patient populations is necessary to optimize implementation of telehealth.

Methods: As part of a Clinical Sequencing Evidence-Generating Research Consortium cross-site study, we assessed satisfaction with mode of return of results (RoR) delivery across a diverse sample of participants receiving genetic testing results in person vs telemedicine (TM).

Results: Ninety-eight percent of participants were satisfied with their mode of results delivery.

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  • Genetic testing, specifically next-generation sequencing (exome and genome sequencing), is being increasingly utilized to identify causes of cardiovascular diseases in infants and children, but the effectiveness of these tests across different types of heart conditions has been poorly researched.
  • In a study involving 500 patients with congenital heart disease (CHD), it was found that genome sequencing yielded significantly more positive diagnostic results than exome sequencing, especially in patients with syndromic heart defects compared to those with isolated defects.
  • The findings indicated varying success rates for diagnosing different subtypes of CHD, with isolated cardiomyopathy showing higher diagnostic rates than isolated CHD, highlighting the importance of genetic testing for understanding pediatric cardiovascular issues.
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  • The DIP2 gene, first found in fruit flies, is crucial for neuron branching and regeneration, with vertebrate versions (DIP2A, DIP2B, and DIP2C) being highly conserved in the central nervous system.
  • Research showed that mutations in DIP2C are linked to developmental delays in expressive language and speech articulation in 23 affected individuals.
  • Alongside developmental issues, some individuals with DIP2C variants also presented with various cardiac defects and minor facial anomalies, highlighting a connection between the gene's loss-of-function and neurocognitive and physical phenotypes.
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Biallelic variants in the OTUD6B gene have been reported in the literature in association with an intellectual developmental disorder featuring dysmorphic facies, seizures, and distal limb abnormalities. Physical differences described for affected individuals suggest that the disorder may be clinically recognizable, but previous publications have reported an initial clinical suspicion for Kabuki syndrome (KS) in some affected individuals. Here, we report on three siblings with biallelic variants in OTUD6B co-segregating with neurodevelopmental delay, shared physical differences, and other clinical findings similar to those of previously reported individuals.

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It has been suggested that diagnostic yield (DY) from Exome Sequencing (ES) may be lower among patients with non-European ancestries than those with European ancestry. We examined the association of DY with estimated continental/subcontinental genetic ancestry in a racially/ethnically diverse pediatric and prenatal clinical cohort. Cases (N = 845) with suspected genetic disorders underwent ES for diagnosis.

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  • - The study explores pre-mRNA splicing, its critical role in neurodevelopment, and how mutations in spliceosome-related genes U2AF2 and PRPF19 contribute to neurodevelopmental disorders (NDDs).
  • - Researchers found multiple pathogenic variants in U2AF2 and PRPF19 across unrelated individuals, with functional analysis showing that specific U2AF2 variants disrupted normal splicing and neuritogenesis in human neurons.
  • - Additionally, investigations in Drosophila models revealed that the loss of function in U2AF2 and PRPF19 caused severe developmental defects and social issues, pointing to a genetic network wherein splicing factors like Rbfox1 play a significant role in brain development and function. *
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In the last few decades, medical genetics has undergone a revolution because of the development of technologies and informatics approaches that can generate and analyze large amounts of genomic data. Pediatricians have been hugely affected by these changes. The early age of presentation for birth defects and neurocognitive disorders, together with a shortage of trained genetics professionals, has increased consultations for conditions with a genetic cause, not only in pediatric practice but also in other subspecialties.

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Background And Objectives: Genomic sequencing (GS) is increasingly used for diagnostic evaluation, yet follow-up care is not well understood. We assessed clinicians' recommendations after GS, parent-reported follow-up, and actions parents initiated in response to learning their child's GS results.

Methods: We surveyed parents of children who received GS through the Clinical Sequencing Evidence Generating Research consortium ∼5 to 7 months after return of results.

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Rubinstein-Taybi syndrome (RSTS) is a rare congenital disorder characterized by developmental and intellectual disability, broadening of thumbs and halluces, and characteristic facial features. Pathogenic variants in lead to RSTS type 1 (RSTS1) and in lead to RSTS type 2 (RSTS2). Individuals with RSTS can demonstrate a variety of behavioral and neuropsychiatric challenges, including anxiety, hyperactivity/inattention, self-injury, repetitive behaviors, and aggression.

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Purpose: It has been hypothesized that diagnostic yield (DY) from Exome Sequencing (ES) may be lower among patients with non-European ancestries than those with European ancestry. We examined the association of DY with estimated continental genetic ancestry in a racially/ethnically diverse pediatric and prenatal clinical cohort.

Methods: Cases (N=845) with suspected genetic disorders underwent ES for diagnosis.

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Article Synopsis
  • The study assessed the effectiveness of exome sequencing (ES) in diagnosing genetic disorders among pediatric and prenatal patients, particularly focusing on underrepresented minority (URM) and underserved (US) populations.
  • The diagnostic yield was found to be 23.8%, with a higher success rate in pediatric patients (26.7%) compared to prenatal patients (19.0%).
  • The results indicated no significant differences in diagnostic yield or inconclusive findings between URM/US and non-URM/non-US patients, highlighting ES's potential for diverse populations.
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Purpose: Accurate and understandable information after genetic testing is critical for patients, family members, and professionals alike.

Methods: As part of a cross-site study from the Clinical Sequencing Evidence-Generating Research consortium, we investigated the information-seeking practices among patients and family members at 5 to 7 months after genetic testing results disclosure, assessing the perceived utility of a variety of information sources, such as family and friends, health care providers, support groups, and the internet.

Results: We found that individuals placed a high value on information obtained from genetics professionals and health care workers, independent of genetic testing result case classifications as positive, inconclusive, or negative.

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Background And Objectives: A previous publication of pregnancy outcomes in onabotulinumtoxinA-exposed mothers demonstrated that the prevalence of major fetal defects (0.9%, 1/110) was comparable with background rates in the general population. There is continued interest to better understand the safety of onabotulinumtoxinA during pregnancy.

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