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Open Access Publications from the University of California

Scholarly Works (14 results)

  • Thesis
  • Peer Reviewed
UC Irvine Electronic Theses and Dissertations (2018)

Several studies have shown that receiving a variant of uncertain significance (VUS) result from genetic testing can invoke confusion or anxiety. This has been explored by studies in the setting of cancer genetics, but not in the setting of genetic testing for inherited cardiomyopathies. This study compared levels of cardiac anxiety, general anxiety, and depression in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) with a pathogenic, negative, or VUS result from genetic testing, as well patients and family members who did not undergo genetic testing. These individuals are enrolled in the ARVC Research Registry at the Johns Hopkins ARVC Program. There was no significant difference in cardiac anxiety between probands with pathogenic, negative and VUS results (p=0.985). Individuals who have not undergone genetic testing had significantly less cardiac anxiety than individuals who have undergone genetic testing, in any result category (p<0.001), but this was likely due to these individuals' status as clinically unaffected family members without implantable cardioverter defibrillators (ICDs). Time elapsed between when an individual received their genetic testing result and when they completed the questionnaire did not have a significant impact on cardiac anxiety (p=0.702), general anxiety (p=0.393) or depression (p=0.683). Overall, genetic test results did not appear to be a major driver for cardiac anxiety, anxiety or depression in this population of ARVC patients and their family members when controlling for other factors such as having an ICD.

    Cover page: Effect of Variants of Uncertain Significance on Anxiety and Depression in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy and their Family Members
    • Thesis
    • Peer Reviewed
    UC Irvine Electronic Theses and Dissertations (2024)

    Previous studies assessing the genetic counseling graduate program (GCGP) application experience have been limited and largely focused on admitted applicants; half of applicants are not admitted annually, but there is a significant gap in the understanding of their experiences. This study aimed to evaluate the factors affecting GCGP selection, barriers in the application process and factors affecting the overall application experience for 2021-2024 GCGP applicants. The factors and barriers affecting various GCGP applicant subgroups were also compared. Of the 377 participants who completed the online survey, 30% were matched, 41% were unmatched, and 28% were first-time applicants in 2024. The top factor influencing GCGP selection across all participants was the cost of tuition (74%), while the cost of individual program applications was a frequently selected barrier in the application process (68%) and a factor influencing the overall application experience (49%).GCGP selection by unmatched applicants was notably influenced by the cost of living in a program’s area when compared to matched applicants (p=0.020). Unmatched applicants also more frequently indicated that obtaining advocacy (p<0.001), volunteer (p=0.002), or research (p=0.007) experience were barriers in the application process, when compared to matched applicants. Matched applicants more frequently reported that exam-related costs were barriers in the application process, when compared to unmatched applicants (p=0.002). One notable theme in this study was diversity. Diversity within the patient, faculty and student populations were each more frequently cited by non-White applicants as factors influencing GCGP selection when compared to White applicants (p<0.001 for all three comparisons). Diversity within the genetic counseling field was also cited more frequently as a barrier by non-White (p<0.001) and LGBTQ2IA+ (p=0.007) applicants when compared to White and non-LGBTQ2IA+ applicants, respectively. In addition, diversity within programs was more frequently selected as a barrier by these two subgroups, when compared to White (p<0.001) and non-LGBTQ2IA+ applicants (p=0.031), respectively. A lack of diversity within programs and the field of genetic counseling was cited more frequently by non-White applicants as affecting their overall application experience when compared to White applicants (p<0.001 for both comparisons). Working to address these factors and barriers, particularly for underrepresented groups in medicine, could advance diversity within the genetic counseling field, guide recruitment strategies, and enhance the match/application process and experience.

      Cover page: Assessing the Factors and Barriers That Affect the Experience of Applicants Participating in the National Matching Services (NMS) Genetic Counseling Match Program
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2014)
      Newly implemented newborn screening (NBS) programs in California have resulted in a large subset of patients in whom at least two cystic fibrosis transmembrane conductance regulator (CFTR) mutations are identified, but subsequent sweat chloride analysis reveals normal or indeterminate values. These patients are diagnosed with CFTR-Related Metabolic Syndrome (CRMS). However, the natural progression and management of these patients are not clearly understood and frequently after the age of 1-year these patients are lost to follow-up with Cystic Fibrosis (CF) Centers. We present the first case of an infant who was referred to Miller Children's Hospital for a NBS positive for CF and subsequent discovery of identical mutations in six of his seven older brothers. Several siblings had positive sweat chloride results on repeat testing after the age of 3 years. We suggest the need for continued follow-up of CRMS in a CF center with diagnostic evaluation including repeat sweat chloride testing, beyond the currently recommended period.
        Cover page: Diagnosis of cystic fibrosis in the kindred of an infant with CFTR‐related metabolic syndrome: Importance of follow‐up that includes monitoring sweat chloride concentrations over time
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2013)

        Purpose

        Nevoid basal cell carcinoma syndrome is an autosomal dominant disorder characterized by multiple basal cell carcinomas, jaw cysts, palmar/plantar pits, spine and rib anomalies, and falx cerebri calcification. Current diagnostic criteria are suboptimal when applied to pediatric populations, as most common symptoms often do not begin to appear until teenage years.

        Methods

        We studied minor and major clinical features in 30 children/teenagers and compared the findings with 75 adults from 26 families with nevoid basal cell carcinoma syndrome.

        Results

        Fifty percent of children/teenagers and 82% of adults had at least one basal cell carcinoma. Jaw cysts occurred in 60% of children/teenagers and 81% of adults. Palmar/plantar pits were the most frequent feature seen in affected individuals at all ages. Macrocephaly was seen in 50% of affected and 8% of unaffected children/teenagers. Frontal bossing, hypertelorism, Sprengel deformity, pectus deformity, and cleft lip/palate were seen among affected children/teenagers but not among their unaffected siblings. Falx calcification, the most frequent radiological feature, was present in 37% of individuals <20 and 79% of those >20 years.

        Conclusion

        We report clinical and radiological manifestations of nevoid basal cell carcinoma syndrome in children/teenagers, many of whom lacked major features such as basal cell carcinomas, jaw cysts, and falx calcification. Evaluations for palmar/plantar pits, craniofacial features, and radiological manifestations permit early diagnosis and optimum surveillance.
          Cover page: Clinical and radiological features in young individuals with nevoid basal cell carcinoma syndromeCreative Commons 'BY' version 4.0 license
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (2011)
          We describe an infant male of Cambodian background who has typical craniofacial features of mycophenolate mofetil (MMF) embryopathy and a complex congenital heart defect (CHD) (double outlet right ventricle, mitral atresia, pulmonic stenosis, and total anomalous pulmonary venous return). Together with four case reports and the 20 patients included in two recent reviews, we report 24 (19 affected, five normal) patients with this pattern of anomalies. Eight (33%) have a CHD, most commonly, conotruncal or aortic arch defects (6/8, 75%). This would support the hypothesis that disturbance of cranial neural crest migration occurs in exposed infants, and may predict which additional anomalies will be observed in the future. We also attempted to score the severity of the facial anomalies in each MMF patient using a system created by plastic surgeons for patients with hemifacial microsomia. This classification had modest utility in comparing severity and correlating facial to extracranial defects. The findings are viewed with caution because of the preliminary methodology. Finally, since several exposed infants have been reported to be minimally affected, we remind clinicians to be sensitive to the potential mild expression of the effects of this teratogen. This awareness may influence clinical management of apparently normal MMF-exposed individuals.
            Cover page: An additional patient with mycophenolate mofetil embryopathy: Cardiac and facial analysesCreative Commons 'BY' version 4.0 license
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (2019)
            ALG11-Congenital Disorder of Glycosylation (ALG11-CDG, also known as congenital disorder of glycosylation type Ip) is an inherited inborn error of metabolism due to abnormal protein and lipid glycosylation. We describe two unrelated patients with ALG11-CDG due to novel mutations, review the literature of previously described affected individuals, and further expand the clinical phenotype. Both affected individuals reported here had severe psychomotor disabilities and epilepsy. Their fibroblasts synthesized truncated precursor glycan structures, consistent with ALG11-CDG, while also showing hypoglycosylation of a novel biomarker, GP130. Surprisingly, one patient presented with normal transferrin glycosylation profile, a feature that has not been reported previously in patients with ALG11-CDG. Together, our data expand the clinical and mutational spectrum of ALG11-CDG.
              Cover page: ALG11-CDG syndrome: Expanding the phenotype.
              • Article
              • Peer Reviewed
              UC Irvine Previously Published Works (2014)
              Purpose: Colorectal cancer (CRC) incidence has decreased over the past three decades, due largely to screening efforts. Relatively little is known about CRC incidence among the young adult (YA) population ages 20-39, as screening typically commences at age 50 for average-risk individuals. We examined CRC incidence with a focus on YAs in order to identify high-risk subgroups. Methods: We analyzed 231,544 incident CRC cases from 1988-2009 (including 5617 YAs 20-39 years of age) from the California Cancer Registry. We assessed age-specific incidence rates by race/ethnicity, gender, and colorectal tumor location, and calculated the biannual percent change (BAPC) to monitor change in incidence over the 22-year study period. Results: The absolute incidence of CRC per 100,000 was low among YAs 20-29 and 30-39 years old (ranging from 0.7 per 100,000 among Hispanic and African American females aged 20-29 up to 5.0 per 100,000 among Asian/Pacific Islander males aged 30-39). However, we observed increasing CRC incidence rates over time among both males and females in the YA population, particularly for distal colon cancer in Hispanic females aged 20-29 (BAPC=+15.9%; p<0.042). Conclusion: The absolute incidence of CRC remains far lower for YAs than among adults aged 50 and over. However, CRC incidence is increasing among young adults, in contrast to the decreasing rates observed for adults in the screened population (aged 50 and above). More research is needed to better characterize YAs at increased risk for CRC.
                Cover page: Colorectal Cancer Incidence Among Young Adults in California.
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2014)
                Cri-du-chat is a rare congenital syndrome characterized by intellectual disability, severe speech/developmental delay, dysmorphic features, and additional syndromic findings. The etiology of this disorder is well known, and is attributed to a large deletion on chromosome 5 that typically ranges from band 5p15.2 to the short arm terminus. This region contains CTNND2, a gene encoding a neuronal-specific protein, delta-catenin, which plays a critical role in cellular motility and brain function. The exact involvement of CTNND2 in the cognitive functionality of individuals with Cri-du-chat has not been fully deciphered, but it is thought to be significant. This report describes an 8-year-old African-American female with a complex chromosome 5 abnormality and a relatively mild case of cri-du-chat syndrome. Because of the surprisingly mild cognitive phenotype, although a karyotype had confirmed the 5p deletion at birth, an oligo-SNP microarray was obtained to further characterize her deletion. The array revealed a complex rearrangement, including a breakpoint in the middle of CTNND2, which resulted in a partial deletion and partial duplication of that gene. The array also verified the expected 5p terminal deletion. Although the patient has a significant deletion in CTNND2, half of the gene (including the promoter region) is not only preserved, but is duplicated. The patient's milder cognitive and behavioral presentation, in conjunction with her atypical 5p alteration, provides additional evidence for the role of CTNND2 in the cognitive phenotype of individuals with Cri-du-chat.
                  Cover page: Amelioration of the typical cognitive phenotype in a patient with the 5pter deletion associated with Cri‐du‐chat syndrome in addition to a partial duplication of CTNND2Creative Commons 'BY' version 4.0 license
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2023)

                  Background

                  Liveborn infants with non-mosaic trisomy 22 are rarely described in the medical literature. Reported lifespan of these patients ranges from minutes to 3 years, with the absence of cardiac anomalies associated with longer-term survival. The landscape for offering cardiac surgery to patients with rare autosomal trisomies is currently evolving, as has been demonstrated recently in trisomies 13 and 18. However, limited available data on patients with rare autosomal trisomies provides a significant challenge in perinatal counseling, especially when there are options for surgical intervention.

                  Case presentation

                  In this case report, we describe an infant born at term with prenatally diagnosed apparently non-mosaic trisomy 22 and multiple cardiac anomalies, including a double outlet right ventricle, hypoplastic aortic valve and severe aortic arch hypoplasia, who underwent cardiac surgery. The decisions made by her family lending to her progress and survival to this day were made with a focus on the shared decision making model and support in the prenatal and perinatal period. We also review the published data on survival and quality of life after cardiac surgery in infants with rare trisomies.

                  Conclusions

                  This patient is the only known case of apparently non-mosaic trisomy 22 in the literature who has undergone cardiac surgery with significant survival benefit. This case highlights the impact of using a shared decision making model when there is prognostic uncertainty.
                    Cover page: Non-mosaic trisomy 22 and congenital heart surgery using the shared decision making model: a case report
                    • Article
                    • Peer Reviewed
                    UC Irvine Previously Published Works (2017)
                    Tricho-Rhino-Phalangeal syndrome is a rare autosomal dominant genetic disorder caused by mutations in the TRPS1 gene. This malformation syndrome is characterized by distinctive craniofacial features including sparse scalp hair, bulbous tip of the nose, long flat philtrum, thin upper vermilion border, and protruding ears. Skeletal abnormalities include cone-shaped epiphyses at the phalanges, hip malformations, and short stature. In this report, we describe two patients with the physical manifestations and genotype of TRPS type I but with learning/intellectual disability not typically described as part of the syndrome. The first patient has a novel heterozygous two-base-pair deletion of nucleotides at 3198-3199 (c.3198-3199delAT) in the TRPS1 gene causing a translational frameshift and subsequent alternate stop codon. The second patient has a 3.08 million base-pair interstitial deletion at 8q23.3 (113,735,487-116,818,578), which includes the TRPS1 gene and CSMD3. Our patients have characteristic craniofacial features, Legg-Perthes syndrome, various skeletal abnormalities including cone shaped epiphyses, anxiety (first patient), and intellectual disability, presenting unusual phenotypes that add to the clinical spectrum of the disease.
                      Cover page: Two cases of Legg–Perthes and intellectual disability in Tricho–Rhino–Phalangeal syndrome type 1 associated with novel TRPS1 mutationsCreative Commons 'BY' version 4.0 license
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