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Seven cases of histoplasmosis have been reported, 6 males and one female. Their ages ranged from 40 to 78 years. Of 7 patients, 5 had skin lesions, 4 with palatal ulcer, one with papules and nodules. None of the patients were HIV positive. In all patients either cytology, or skin biopsy or both revealed Histoplasma. Culture was positive in two patients.

In the present study, skin biopsies in suspected cases of deep fungal infections were subjected to H &E and special stainings. In 2 of the 5 cases of sporotrichosis and in both cases of chromomycosis and of histoplasmosis, PAS positive fungal elements could be demonstrated. In both the cases of histoplasmosis, the fungi were also demonstrated by GMS staining. In 3 cases of sporotrichosis, 2 cases of mycetoma and 3 cases of subcutaneous phycomycosis, fungus could not be demonstrated by PAS staining. However, the histopathological features were corroborative.

In the present study, skin biopsies were analysed for histopathological (HP) changes in 22 patients with various granulomatous dermatoses. In 6 specimens, HP features were diagnostic of BT leprosy, in 1 each of BB, BL and historid LL. The HP features were was lupus valugaris (LV) in 6 biopsies, tuberculosis verrucosa cutis (TBVC) in 2, sarcoidosis in 3 and sporotrichosis in remaining 2. The study reiterated the usefulness of HP examination of all suspected cases of granulomatous skin diseases.

Fourteen patients, 8 girls and 6 boys with trachyonychia have been reported. Their ages ranged from 5 to12 years; mean 8.5 years. All of them had retarded growth of nail plates with roughness. Fragility blackish discoloration, longitudinal ridging of all the 20 nails of fingers and toes. Six patients had thickening of the nail plates while 8 had thinning. In one patient each oil drop sign and splinter haemorrhages were seen; two patients each had associated lichen planus and psoriasis and one each atopic dermatitis, vitiligo and alopecia areata. Personal history of atopy was obtained in 6 patients. Nail biopsy carried out in 5 patients revealed nonspecific histology. Radiological examination of fingers and toes revealed no bony or joint abnormality. The nail changes remained almost static during a 4 year follow-up period.

Biallelic pathogenic variants in MAP3K20, which encodes a mitogen-activated protein kinase, are a rare cause of split-hand foot malformation (SHFM), hearing loss, and nail abnormalities or congenital myopathy. However, heterozygous variants in this gene have not been definitively associated with a phenotype. Here, we describe the phenotypic spectrum associated with heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20. We report five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in this specific region of the gene. These individuals exhibit both shared and unique clinical manifestations, highlighting the complexity and variability of the disorder. We propose that the involvement of MAP3K20 in endothelial-mesenchymal transition provides a plausible etiology of these features. Together, these findings characterize a disorder that both expands the phenotypic spectrum associated with MAP3K20 and highlights the need for further studies on its role in early human development., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: No consensus germline testing guidelines currently exist for glioma patients, so the prevalence of germline pathogenic variants remains unknown. This study aims to determine the prevalence and type of pathogenic germline variants in adult glioma., Methods: A retrospective review at a single institution with paired tumor/normal sequencing from August 2018-April 2022 was performed and corresponding clinical data were collected., Results: We identified 152 glioma patients of which 15 (9.8%) had pathogenic germline variants. Pathogenic germline variants were seen in 11/84 (13.1%) of Glioblastoma, IDH wild type; 3/42 (7.1%) of Astrocytoma, IDH mutant; and 1/26 (3.8%) of Oligodendroglioma, IDH mutant, and 1p/19q co-deleted patients. Pathogenic variants in BRCA2 , MUTYH, and CHEK2 were most common (3/15, 20% each). BRCA1 variants occurred in 2/15 (13%) patients, with variants in NF1 , ATM , MSH2 , and MSH3 occurring in one patient (7%) each. Prior cancer diagnosis was found in 5/15 patients (33%). Second-hit somatic variants were seen in 3/15 patients (20%) in NF1 , MUTYH, and MSH2 . Referral to genetics was performed in 6/15 (40%) patients with pathogenic germline variants. 14/15 (93%) of patients discovered their pathogenic variant as a result of their paired glioma sequencing., Conclusions: These findings suggest a possible overlooked opportunity for determination of hereditary cancer syndromes with impact on surveillance as well as potential broader treatment options. Further studies that can determine the role of variants in gliomagenesis and confirm the occurrence and types of pathogenic germline variants in patients with IDH wild type compared to IDH mutant tumors are necessary., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: In 2011, we introduced an innovative parallel curriculum at Baylor College of Medicine, formerly called the Genetics Track Curriculum and now called the Genetics and Genomics Pathway, aimed at providing an opportunity for an enriched educational experience throughout medical school. In this report, we describe our 10-year experience with the program and highlight growth in enrollment as well as academic achievements of graduating students., Methods: We reviewed the data of students enrolled in this pathway, including retention, satisfaction, student-driven curriculum changes, scholarly outcomes, and career outcomes., Results: From September 2011 to June 2021, 121 students were enrolled in the Genetics and Genomics Pathway program. In total, 64 students (64/121 = 53%) left the program before graduating (the majority, after their first year). Of the 57 remaining students, 29 graduated (29/57, approximately 51%), and 4 of the 29 students (4/29 = 14%) matched into a genetics training program., Conclusion: This novel program serves as a mechanism for garnering increased interest and competence in medical genetics. The longitudinal nature of the program fosters enthusiasm for genetics and provides ample opportunity to develop valuable research skills. Given the ongoing shortage of providers in this field, such programs are vital to increase the size of the workforce and broaden the knowledge of providers in diverse fields., Competing Interests: Conflict of Interest All authors, at the time of this study, were employees of Baylor College of Medicine, which has a partnership with Baylor Genetics that derives revenue from clinical testing., (Published by Elsevier Inc.)

The American Academy of Pediatrics, the American College of Medical Genetics and Genomics, and the American Academy of Neurology recommend genetic testing, as a genetic evaluation tool, for children diagnosed with autism spectrum disorders (ASD). Despite the potential benefits, the utilization of genetic testing is low. We proposed an integrated theoretical framework to examine parents' intention and associated psychosocial factors in pursuing genetic testing for their children with ASD. Recruiting primarily from the Interactive Autism Network, a nationwide sample of 411 parents of children with ASD who had never pursued genetic testing for their children completed our theory-based online survey. Data were analyzed using structural equation modeling. About half of the parents were willing to pursue genetic testing for their children with ASD. Findings of the structural equation modeling suggested a good model fit between our integrated theoretical framework and survey data. Parents' intention was significantly and positively associated with their attitudes toward genetic testing, subjective norm, and self-efficacy in having their children tested. This study serves as an initial window to understand parental intention to pursue genetic testing for their children with ASD. Our findings can help physicians and genetic counselors understand, educate, counsel, and support parents' decision-making about having their children with ASD genetically tested. Furthermore, our study can also assist physicians and genetic counselors in developing theory- and evidence-based patient education materials to enhance genetic testing knowledge among parents of children with ASD., (© 2020 National Society of Genetic Counselors.)

Due to the increased prevalence of Autism Spectrum Disorder (ASD), more children with ASD may be referred for genetic testing. It is important to develop a tool to help parents consider the benefits and drawbacks of genetic testing for ASD before pursuing genetic testing for children with ASD. We developed the first theory-based survey-Perceptions of ASD Genetic Testing Survey (POAGTS), as a tool to assist healthcare providers to better understand parents' perceptions and concerns regarding ASD genetic testing. The psychometric properties of POAGTS were first pre-tested and then formally tested with 308 parents of children with ASD who had not decided whether to pursue genetic testing for their children diagnosed with ASD. Findings suggest that the eight scales of the POAGTS were psychometrically sound, and had acceptable data reliability and validity. Additional research with various samples, such as parents of children with ASD who belong to diverse racial/ethnic and socioeconomic groups, is warranted in the future to determine whether the POAGTS is applicable to these particular groups. Condensing and refining this tool to a shorter, more user-friendly version is also recommended for future research.

Cancer is the second leading cause of death in the U.S. Utilizing family health history in cancer prevention holds promise in lessening the burden of cancer. Nevertheless, family health history is underutilized in public health and preventive medicine. Community health workers, also known as lay health educators, are ideal candidates to offer basic cancer family history-based education and services to the general public. The authors developed the first cancer family history-based genomics training program in cancer prevention tailored for community health workers. This paper details the development and pilot testing findings of the training. Specifically, a multidisciplinary research team of geneticists, genetic counselors, health educators, community health workers, and community health worker instructors developed a 7-module, 6-hour, bilingual (English and Spanish) cancer family history-based training focusing on cancer family history-based risk assessment, lifestyle recommendations, and genetic evaluation and testing. The curriculum was based on an integrated theoretical framework, the National Comprehensive Cancer Network guidelines, the community health worker core competencies, and the 4MAT instructional model. The Texas Department of State Health Services approved and certified the curriculum with 2 delivery formats: in-person/face-to-face workshops and online training. A total of 34 community health workers completed the pilot training in person (n=17) and online (n=17) in 2018 and 2019. Participating community health workers' knowledge, attitudes, self-efficacy, and intention in delivering basic cancer family history-based genomics education and services significantly increased on the immediate post-test measures compared with their pretest data. Positive ratings and feedback were also reported by the community health workers. Findings from this pilot study suggest that wider training is warranted for educating more community health workers in the U.S., (Copyright © 2020 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Health educators (HEs), who are specialized in health education, can provide basic genomics education/services to the public. Such practice of HEs is unknown. We examined HEs' genomics knowledge and practice, intention, attitudes, self-efficacy and perceived barriers in providing basic genomics education/services. Materials & methods: Texas HEs (n = 662) were invited to complete the survey that was developed based on theoretical constructs (i.e., practice/behavior, intention, attitudes, self-efficacy, knowledge and perceived barriers) from various health behavior theories. Results: Among 182 HEs completed the survey, most had never/seldom provided basic genomics education/services. Participants' practice was positively associated with their intention in performing basic genomics education/services and previous genomics training. Intention to offer such education/services was positively related to HEs' self-efficacy and attitudes, which were correlated to previous genomics training. Conclusion: Texas HEs lacked basic genomics education/services practice. As previous genomics training was associated with HEs' practice, providing continuing education may enhance their practice.

A genetic evaluation may lead to a clinical or molecular diagnosis, which helps clarify prognosis, tailor surveillance protocols based on risks associated with the genetic condition, and aid in assessment of risk to family members. However, individuals of low socioeconomic and/or minority status often have limited access to genetics services, which contributes to healthcare disparities (Journal of Community Genetics, 2018, 9, 233). Our county hospital system, dedicated to providing health care to the underserved, offers a unique opportunity to reduce healthcare inequalities in genetics. This retrospective chart review included 2,304 patients evaluated at an outpatient county hospital genetics clinic between January 1, 2013, and December 31, 2018, during which time genetic testing was recommended for most patients (58.5%) for a total of 1,429 recommended genetic tests. Most tests were obtained through non-hospital financial resources (56.5%), and loss to follow-up during the phlebotomy stage was the most common reason for tests not to be ordered (41.9%) and not to be completed (36.4%). The experience in our clinic suggests that identifying financial avenues, such as commercial laboratory financial assistance programs in addition to county hospital funds, can support obtaining genetic testing and allow healthcare providers to overcome financial barriers to genetic testing., (© 2020 National Society of Genetic Counselors.)

Introduction: Case-based learning (CBL) is a pedagogical method using clinical case studies to reinforce learning topics. A pilot elective course incorporating CBL was offered for first-year medical students. The purpose of this study is to (1) describe the logistics of implementing the course and (2) evaluate its reception among medical students on its efficacy in learning basic science class material., Method: An 8-week elective course was offered to medical students from 2012 to 2017. Specialists facilitated case discussions synthesizing material from didactic lectures with clinical scenarios. End-of-term surveys with multiple choice and free response questions were distributed to students and described using summary statistics., Results: There were 13 cohorts of enrollees, and the average number of students enrolled per cohort was 45.6, out of an average class size of 186 (24.5%, range 36-60). One hundred ninety-eight (64.2%) students reported that the course considerably changed or greatly expanded knowledge. Three hundred two (89.1%) students felt it met a majority of or exceeded expectations. Two hundred eighty-seven (80.2%) responses indicated interest in taking the course again or recommending it to others. One hundred six responses (27.1%) indicated preference for CBL over traditional lectures, and 177 (45.3%) were interested to see CBL integrated into the curriculum., Conclusions: Overall, this CBL elective course was well-received and perceived as effective for better learning class material by students. Additionally, students were receptive to case-based learning and integrating this style of learning into a preclinical curriculum without entirely replacing didactic-based learning. These findings may encourage more medical schools to explore incorporating CBL in the curriculum., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© International Association of Medical Science Educators 2020.)

This study examined the experiences of Autism Spectrum Disorder (ASD) genetic testing among parents of children with ASD. A nationwide sample of 552 parents of children with ASD completed an online survey. Nearly one-quarter (22.5%) of the parents reported that their affected children had undergone ASD genetic testing. The testing utilization was associated with awareness of ASD genetic testing and whether information was received from healthcare providers. Among parents whose children with ASD were tested, 37.6% had negative experiences, which mainly due to lack of perceived testing benefits to their affected children and unpleasant testing experiences with healthcare providers. To provide better healthcare services, it is critical to ensure parents understand the purposes, benefits, and results of ASD genetic testing.

Postsynaptic density (PSD) proteins have been implicated in the pathophysiology of neurodevelopmental and psychiatric disorders. Here, we present detailed clinical and genetic data for 20 patients with likely gene-disrupting mutations in TANC2-whose protein product interacts with multiple PSD proteins. Pediatric patients with disruptive mutations present with autism, intellectual disability, and delayed language and motor development. In addition to a variable degree of epilepsy and facial dysmorphism, we observe a pattern of more complex psychiatric dysfunction or behavioral problems in adult probands or carrier parents. Although this observation requires replication to establish statistical significance, it also suggests that mutations in this gene are associated with a variety of neuropsychiatric disorders consistent with its postsynaptic function. We find that TANC2 is expressed broadly in the human developing brain, especially in excitatory neurons and glial cells, but shows a more restricted pattern in Drosophila glial cells where its disruption affects behavioral outcomes.

Understanding parents' educational needs concerning genetic testing for their children with autism spectrum disorder (ASD) is important in developing tailored, evidence-based health education materials for clinical use. Since research is lacking in this area, to bridge the gap, we examined genetic testing education needs using a nationwide sample of parents of biological children with ASD in the United States. Prospective participants were recruited from the interactive autism network, and 552 parents of biological children with ASD completed the online survey. Most participants (73.7%) were interested in receiving health education about genetic testing. Yet, the majority of them (64.7%) reported that they did not receive the information needed from physicians. Parents who identified as racial/ethnic minorities (P = 0.029), who had an education degree below college (P = 0.002), or displayed low/no awareness of genetic testing (P = 0.003) were more interested in receiving health education regarding genetic testing. Parents' most desired topics for health education include the accuracy of genetic testing (88.4%), cost (85.9%), relevant benefits of such testing (83.8%), testing procedure (77.8%), eligibility to undergo genetic testing for their children with ASD (62.4%), potential harms caused by genetic testing (56.1%), previous use and experience among individuals affected by ASD (50.8%), and confidentiality issues (48.0%). Furthermore, web-based education was the preferable approach (85.4%). Our findings can help develop health education programs and/or materials regarding genetic testing for parents and physicians to facilitate better physician-parent communication and assist parents in making informed medical decisions regarding genetic testing. Autism Res 2019, 12: 1162-1170. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study examined educational needs on genetic testing among 552 American parents of children with autism spectrum disorder (ASD). Results showed that most parents expressed interests in receiving health education regarding genetic testing (73.7%) and favored online education resources (85.4%). Preferred topics included accuracy, cost, and testing benefits. Our findings can help develop genetic testing related health education programs and materials for parents of children with ASD., (© 2019 International Society for Autism Research, Wiley Periodicals, Inc.)

DNM1L encodes a GTPase of the dynamin superfamily, which plays a crucial role in mitochondrial and peroxisomal fission. Pathogenic variants affecting the middle domain and the GTPase domain of DNM1L have been implicated in encephalopathy because of defective mitochondrial and peroxisomal fission 1 (EMPF1, MIM #614388). Patients show variable phenotypes ranging from severe hypotonia leading to death in the neonatal period to developmental delay/regression, with or without seizures. Familial pathogenic variants in the GTPase domain have also been associated with isolated optic atrophy. We present a 27-yr-old woman with static encephalopathy, a history of seizures, and nystagmus, in whom a novel de novo heterozygous variant was detected in the GTPase effector domain (GED) of DNM1L (c.2072A>G, p.Tyr691Cys). Functional studies in Drosophila demonstrate large, abnormally distributed peroxisomes and mitochondria, an effect very similar to that of middle domain missense alleles observed in pediatric subjects with EMPF1. To our knowledge, not only is this the first report of a disease-causing variant in the GED domain in humans, but this is also the oldest living individual reported with EMPF1. Longitudinal data of this kind helps to expand our knowledge of the natural history of a growing list of DNM1L -related disorders., (© 2019 Assia Batzir et al.; Published by Cold Spring Harbor Laboratory Press.)

Background: Genetic providers face the challenge of having adequate time to conduct a comprehensive evaluation. Hypermobile Ehlers-Danlos (hEDS) syndrome has a complex array of symptoms. An initial visit can involve approximately 60-80 min and an additional 45 min for the check-in and checkout process. We propose a model to improve clinic flow and patient satisfaction by using: (a) pre-appointment questionnaire (b) disease information sheet outlining basic management and (c) itinerary detailing the visit., Methods: New patients were given a questionnaire, an EDS information sheet, and a visit itinerary. In the end, a patient satisfaction survey was administered containing 18 questions pertaining to their satisfaction with the questionnaire, the information sheet, and their overall visit. Completed surveys were turned in to the front desk to maintain anonymity., Results: Based on the survey results, patient satisfaction toward the implementation of a questionnaire was overwhelmingly positive. Survey responders found that the itinerary was added to their understanding of the appointment process and that the hEDS information sheets were helpful, understandable, and appropriate in length. Respondents said that they strongly agreed or agreed with the following statements: (a) I was satisfied with the visit; (b) I now have a better understanding of my condition; (c) This visit was successful in addressing my most pressing concerns; and (d) I would recommend this clinic to others., Conclusion: Designing a disease-centered model that implements patient-centered resources improves patient understanding and satisfaction for new hEDS patient visits. This model can be emulated in diagnosis and management of other complex genetic and nongenetic conditions., (© 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Purpose: Genomics services have the potential to reduce incidence and mortality of diseases by providing individualized, family health history (FHH)-based prevention strategies to clients. These services may benefit from the involvement of community health workers (CHWs) in the provision of FHH-based genomics education and services, as CHWs are frontline public health workers and lay health educators, who share similar ethnicities, languages, socioeconomic statuses, and life experiences with the communities they serve. We developed, implemented, and evaluated the FHH-based genomics training program for CHWs., Methods: This theory- and evidence-based FHH-focused genomics curriculum was developed by an interdisciplinary team. Full-day workshops in English and Spanish were delivered to 145 Texas CHWs (91.6% were Hispanic/black). Preworkshop, postworkshop, and 3-month follow-up data were collected., Results: CHWs significantly improved their attitudes, intention, self-efficacy, and knowledge regarding adopting FHH-based genomics into their practice after the workshops. At 3-month follow-up, these scores remained higher, and there was a significant increase in CHWs' genomics practices., Conclusion: This FHH-based genomics training successfully educated Texas CHWs, and the outcomes were promising. Dissemination of training to CHWs in and outside of Texas is needed to promote better access to and delivery of personalized genomics services for the lay and underserved communities.

Objective: Leading health agencies recommend physicians to provide information regarding genetic testing for autism spectrum disorders (ASD) to parents of affected children. How to effectively provide this information, however, is unclear for physicians. This qualitative study examined the information needs regarding ASD genetic testing among parents of affected children., Methods: Semi-structured, in-depth interviews were conducted with 42 parents who had at least one child with ASD. Content analysis was utilized to analyze the interview data., Results: The majority of parents (83%) reported they had never received information regarding ASD genetic testing from their doctors. Nevertheless, most parents (86%) expressed an interest to learn about this information. Their preferred topics included: cost (60%), benefits (48%), accuracy (38%), test procedure (29%), potential physical harms from the test (29%), confidentiality (12%), previous utilization by other affected families (2%), and eligibility criteria for this genetic testing (2%). Moreover, parents mentioned various methods to facilitate their learning, including Web-based approaches (43%), workshops/seminars (36%), brochures and flyers (31%), and videos (10%)., Conclusion: To promote parental informed decision-making regarding ASD genetic testing, educational materials should be developed based on our findings., Practice Implications: Application of these needs assessment findings will subsequently improve the delivery of healthcare services., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

In Taiwan, autism spectrum disorders (ASDs) are an emerging public health concern. The ongoing scientific progress for understanding the genetic etiology of ASD makes it increasingly important to examine how parents of children with ASD perceive the causes and recurrence risk of having another child with ASD. These perceptions may influence their family planning, attitudes toward genetic services, and willingness to take their children for ASD genetic testing. However, previous studies addressing this issue were conducted primarily in Western countries. As culture might shape an individual's views of genetic/genomic disorders, this first-of-its-kind study examined the perceptions of the genetic etiology for ASD and the recurrence risk among Taiwanese parents of children affected with ASD. In-depth, semi-structured interviews were conducted among 39 parents having at least one child with ASD. Although the majority of participants believed that ASD has a genetic link, less than half perceived genetic factors as the cause of their own child's ASD. Moreover, most participants articulated their recurrence risk incorrectly. Some parents were concerned about their doctors' limited genomic competencies. To provide parents with better education, counseling, and support for making reproductive decisions, ASD-related genomic education among Taiwanese physicians is needed., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In the United States, prenatal genetic testing (PGT) for Autism Spectrum Disorders (ASD) is currently available via clinical genetic services. Such testing may inform parents about their unborn child's risk for ASD, prepare parents for the birth of an affected infant, and allow them to arrange for early interventions. Although PGT for autism has potential benefits, the associated ethical, legal, and social implications (ELSI) should be considered. This first qualitative study employed a hypothetical scenario to explore the attitudes toward PGT and termination decisions of 42 parents of children with ASD. Over half of the participants expressed willingness to undergo PGT for autism. Reasons included better preparation for birth, early and better treatment, termination of affected pregnancy, contribution to research, and curiosity. Of the 31 parents who were either willing or unsure about undergoing the PGT, approximately three-fourths would continue their hypothetical affected pregnancies. Explanations included preparation for birth of the child, bonding or acceptance of existing ASD-affected children, apprehensions about test limitations, and religious concerns. Parents who reported they would terminate the affected pregnancy in this hypothetical situation were primarily Asians. This study contributes to the growing understanding of the ELSI aspects of PGT in clinical practice., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: The goal of this first-of-its-kind qualitative study was to examine the awareness, attitudes, and experiences among parents of autistic children regarding autism genetic testing., Methods: We conducted in-depth, individual, and semistructured interviews with 42 parents of autistic children with diverse racial/ethnic backgrounds. All interviews were audio-taped, transcribed, and coded into major themes and subthemes., Results: Approximately one-quarter of participants had two or more autistic children, and about half of them were ethnic/racial minorities. The majority of participants postulated favorable attitudes toward autism genetic testing for three main reasons: early intervention and treatment, identifying the etiology of autism, and informed family planning. Nevertheless, among parents who had taken their children for genetic testing, some expressed frustration and questioned the competency of their providers in interpreting test results. Asian parents and those with a low socioeconomic status expressed lower awareness and tended to have more limited access to autism genetic testing., Conclusion: As health-care providers play a vital role in providing genetic services and education, these professionals should be educated and be sensitive to the needs of parents with autistic children. Further quantitative research is required to examine the effects of socio-demographic factors on parents' awareness, attitudes, and experiences regarding autism genetic testing.

The purpose of our study is to familiarize the reader with genetic disorders commonly seen in adults and identify challenges and barriers that limit provision of services. We conducted a retrospective chart analysis of patients seen in the adult Genetics clinics from January 2004 to December 2010 in a metropolitan medical center consisting of an academic private clinic and a county hospital clinic. During the study period, a total of 1,552 patients (n = 1,108 private clinic patients; n = 444 county clinic patients) were evaluated and managed. Of these, 790 and 280 were new patient visits at the private clinic and county clinic, respectively. Approximately 35% (374/1,070) of new patients were seen for cancer-related indications, while neurological indications accounted for approximately 14% (153/1,070) in both clinics. Cardiology-related indications accounted for approximately 13% (145/1,070) of patients, followed closely by chromosomal and syndromic indications for which almost 9% (96/1,070) of new patients were seen. Approximately 8% (90/1,070) of new patients were seen for musculoskeletal indications. We saw increased clinic growth during the study period and found that the most common indications for referral are: (1) Personal/family history of cancer (2) neurological (3) cardiovascular (CV) (4) chromosomal/syndromic and (5) musculoskeletal. A number of challenges were identified, including coordination of services, feasibility of testing, and an overall higher complexity of care with increased clinic scheduling time requirements. Through this review, we demonstrate the demand for adult genetics services and propose some guidelines to address the challenges of management in the adult genetics patient population., (Copyright © 2012 Wiley Periodicals, Inc.)

Sensenbrenner syndrome and unclassified short rib-polydactyly conditions are ciliopathies with overlapping phenotypes and genetic heterogeneity. Mutations in WDR35 were identified recently in a sub-group of patients with Sensenbrenner syndrome and in a single family that presented with an unclassified form of short-rib polydactyly (SRP) syndrome. We report on siblings with an unusual combination of phenotypes: narrow thorax, short stature, minor anomalies, developmental delay, and severe hepatic fibrosis leading to liver failure and early death in two of the children. Both parents were unaffected suggesting autosomal recessive inheritance. The family and their affected children were followed over a decade. Exome sequencing was performed in one affected individual. It showed a homozygous missense mutation in a highly conserved position of the WDR35 gene. This family represents a WDR35-ciliopathy with a complex clinical presentation that includes significant overlap of the phenotypes described in Sensenbrenner syndrome and the unclassified SRPs. The accurate molecular diagnosis of this family exemplifies the power of exome sequencing in the diagnosis of Mendelian disorders and enabled us to broaden and refine our understanding of Sensenbrenner syndrome and SRP. Detailed genotype-phenotype information is provided as well as discussion of previously reported cases., (Copyright © 2012 Wiley Periodicals, Inc.)

Mutations in POLG account for one of the most frequent nuclear encoded causes of mitochondrial disorders to date. Individuals harboring POLG mutations exhibit fairly heterogeneous clinical presentations leading to increasing difficulties in classifying these patients into defined clinical phenotypes. This study aims to investigate the molecular basis of a mitochondrial cytopathy in a patient with 3-methylglutaconic aciduria and to expand the clinical phenotype associated with POLG mutations. Clinical, molecular and genetic analyses as well as neurophysiological examinations were carried out for a 23-year-old woman of mixed Caucasian and Latin American ancestry with a history of cataracts diagnosed at age 1 year, she had onset of distal muscle weakness at age 2 years progressing to atrophy and ovarian dysgenesis at puberty. The patient was found to have 3-methylglutaconic acid with normal 3 hydroxyisovaleric acid on urine organic acid analysis. POLG sequencing was done and a heterozygous variant, c.2851T>A (p.Y951N) was found which is predicted to be deleterious. There are limited reports of POLG mutations in individuals with 3-methylglutaconic aciduria. This case report of a young woman with a heterozygous mutation in POLG, presenting with muscle weakness and atrophy at a young age aims to aid clinicians in similar challenging diagnostic situations as well as enhances our understanding of POLG-related disease phenotypes., (Published by Elsevier B.V.)

Purpose: Physicians entering medical practice in the 21st century will require more than a basic understanding of human genetics because of rapid progress in the field of genetics and genomics. The current undergraduate medical curriculum at most institutions is not adequate to prepare medical students for these challenges. Enhancing exposure to genetics throughout the medical school curriculum should help prepare the next generation of physicians to use genetic and genomic information for optimal patient care., Methods: We have introduced a Genetics Track Curriculum to the undergraduate medical curriculum at Baylor College of Medicine., Results: This track runs in parallel to the existing 4-year curriculum and includes didactic sessions, small group discussions, longitudinal clinical experiences, clinical and laboratory rotations, community outreach, and scholarly projects related to genetics. It also provides the students a means to network and discuss topics and career paths in medical genetics., Conclusion: We have developed a novel curriculum that enhances genomic education for medical students with the ultimate goal of enabling our graduates to deliver more effective and personalized medical care. We believe that the Genetics Track Curriculum at Baylor College of Medicine can serve as a prototype for other medical schools across the country and abroad.

Objective: To present the outcome of a comprehensive team approach to provide genetic evaluation and testing for a large cohort of children diagnosed with retinoblastoma., Methods: The multidisciplinary team included pediatric oncologists, an ophthalmologist, an ophthalmic pathologist, a geneticist, and genetic counselors. Retrospective data from 8 years included 90 initial evaluations, of which 81 probands were diagnosed with retinoblastoma (34 bilateral and 47 unilateral) and 9 were evaluated because of a positive family history., Results: Genetic testing was accomplished equivalently in bilateral and unilateral cases in 51 of 81 patients (63%). In 5 of 30 patients (17%), with unilateral disease an RB1 mutation was identified in peripheral blood samples. In another 7 of 30 patients (23%), mutation analysis confirmed the occurrence of sporadic retinoblastoma. Overall, genetic testing of 48 at-risk family members from 21 families revealed 6 individuals positive and 42 negative for the familial mutation., Conclusions: Our study emphasizes that genetics can be incorporated into the management plan of all retinoblastoma patients using a team approach to ensure timely evaluations and appropriate counseling. Genetic evaluations improved risk prediction for patients and family members as well as prevented overutilization of clinical screening tests, which had potential morbidity for relatives documented to not carry an RB1 mutation.

Complex genomic rearrangements (CGRs) consisting of two or more breakpoint junctions have been observed in genomic disorders. Recently, a chromosome catastrophe phenomenon termed chromothripsis, in which numerous genomic rearrangements are apparently acquired in one single catastrophic event, was described in multiple cancers. Here, we show that constitutionally acquired CGRs share similarities with cancer chromothripsis. In the 17 CGR cases investigated, we observed localization and multiple copy number changes including deletions, duplications, and/or triplications, as well as extensive translocations and inversions. Genomic rearrangements involved varied in size and complexities; in one case, array comparative genomic hybridization revealed 18 copy number changes. Breakpoint sequencing identified characteristic features, including small templated insertions at breakpoints and microhomology at breakpoint junctions, which have been attributed to replicative processes. The resemblance between CGR and chromothripsis suggests similar mechanistic underpinnings. Such chromosome catastrophic events appear to reflect basic DNA metabolism operative throughout an organism's life cycle., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The National Comprehensive Cancer Network (NCCN) has published guidelines for hereditary breast and ovarian cancer syndrome (HBOCS) management. Little data exist on compliance with these guidelines among different physician specialties. We performed an on-line case-based survey by randomly sampling physicians from five specialties, Family Medicine (FM), Obstetrics and Gynecology (OG), General Surgery (GS), Internal Medicine (IM), and Hematology and Oncology (HO). The physicians (n = 225) were asked to provide HBOCS management of healthy women ages 40-42 in the presence of a familial BRCA1 mutation. For women negative for the BRCA1 mutation, 59% of the physicians recommended appropriate surveillance although with significant differences among specialties; P = 0.01. Using an aggregate screening intensity score, physicians clearly recommended more intense screening for mutation positive than negative women (P < 0.0001), but only 16% of physicians followed NCCN guidelines for BRCA1-positive women. Seventy-six percent of all physicians recommended breast MRI with significant variation among specialties ranging from 62% of FM to 89% of OG (P = 0.0020). Similarly, 63% of physicians recommended prophylactic oophorectomy, with 76 and 78% of GS and OG compared to 38% of IM (P < 0.0001) and 57% recommended prophylactic mastectomy ranging from 84% of HO to 32% of FM (P < 0.0001). Independent of specialty, respondents with BRCA testing experience recommended more intense management than those without; P = 0.021. Management recommendations of BRCA1 mutation carriers are not consistent with NCCN guidelines and vary by medical specialty and genetic testing experience. Targeted education of physicians by specialty is needed, so that optimal management is offered to these high-risk women.

Purpose: Sequence-based cancer susceptibility testing results are described as negative, deleterious mutation or variant of uncertain significance. We studied the impact of different types of test results on clinical decision making., Methods: Practicing physicians from five specialties in Texas completed an online case-based survey (n = 225). Respondents were asked to make genetic testing and management recommendations for healthy at-risk relatives of patients with cancer., Results: When the patient carried a deleterious BRCA1 mutation or variant of uncertain significance, 98% and 82% of physicians, respectively, recommended testing of at-risk relatives (P < 0.0001). In both situations, comprehensive BRCA1/2 analysis was selected most with a corresponding 9-fold increase in unnecessary genetic testing costs. There was no difference in physicians with (n = 81) or without (n = 144) prior BRCA1/2 testing experience (P = 0.3869). Cancer risk management recommendations were most intense for the relative with a deleterious mutation compared with variant of uncertain significance, negative, or no testing with 63%, 13%, 5%, and 2%, respectively, recommending oophorectomy (P < 0.0001)., Conclusions: Independent of experience, or specialty, physicians chose more comprehensive testing for healthy relatives than current guidelines recommend. In contrast, management decisions demonstrated the uncertainty associated with a variant of uncertain significance. Utilization of genetic professionals and education of physicians on family-centered genetic testing may improve efficacy and substantially reduce costs.

We report here on a 25-year follow-up of cranio-meta-diaphyseal dysplasia in a 31-year-old Caucasian male, who was reported in the literature at the age of 8 years [Langer et al. (1991); Skeletal Radiol 20:37-41]. He has hyperostotic craniofacial features with protruding lower jaw and midface hypoplasia. He has the typical radiographic features of wide long tubular bones without normal metaphyseal flaring and wide short tubular bones without normal diaphyseal constriction. We describe here his clinical and radiological findings and compare his case with those published in the literature. He is the oldest reported patient with this disorder giving some insight into the natural history of this rare skeletal dysplasia.

The 22q13.3 deletion syndrome results from loss of terminal segments of varying sizes at 22qter. Few genotype-phenotype correlations have been found but all patients have mental retardation and severe delay, or absence of, expressive speech. We carried out clinical and molecular characterization of 13 patients. Developmental delay and speech abnormalities were common to all and comparable in frequency and severity to previously reported cases. Array-based comparative genomic hybridization showed the deletions to vary from 95 kb to 8.5 Mb. We also carried out high-resolution 244K array comparative genomic hybridization in 10 of 13 patients, that defined the proximal and distal breakpoints of each deletion and helped determine the size, extent, and gene content within the deletion. Two patients had a smaller 95 kb terminal deletion with breakpoints within the SHANK3 gene while three other patients had a similar 5.5 Mb deletion implying the recurrent nature of these deletions. The two largest deletions were found in patients with ring chromosome 22. No correlation could be made with deletion size and phenotype although complete/partial SHANK3 was deleted in all patients. There are very few reports on array comparative genomic hybridization analysis on patients with the 22q13.3 deletion syndrome, and we aim to accurately characterize these patients both clinically and at the molecular level, to pave the way for further genotype-phenotype correlations. (c) 2010 Wiley-Liss, Inc.

Various forms of pigmentary dysplasias have been known to be associated with chromosomal mosaicism. One of these disorders, known as phylloid hypomelanosis, has been found to be predominantly associated with abnormalities in chromosome 13. Most of the reported literature involves mosaic trisomy 13 with clinical evidence of abnormal pigmentation in the form of leaf-like or oblong achromic macules following Blaschko's lines. Here, we report on an 8-year-old girl with phylloid hypomelanosis and precocious puberty who was found to have mosaicism for tetrasomy 13q in the form of inverted dup(13)(q21) on her skin fibroblasts as well as peripheral blood karyotype. A higher resolution (244K) chromosomal microarray was done on DNA from skin fibroblasts confirming the breakpoint and gain of distal 13q, which made her tetrasomic for 13q21-qter. This is the first-ever reported association of tetrasomy 13q with phylloid hypomelanosis and precocious puberty. Our report further emphasizes the need to exclude any type of abnormalities of chromosome 13 in patients with phylloid hypopigmentation.

Guanidinoacetate methyltransferase (GAMT) deficiency is a disorder of creatine biosynthesis, characterized by excessive amounts of guanidinoacetate in body fluids, deficiency of creatine in the brain, and presence of mutations in the GAMT gene. We present here 8 new patients with GAMT deficiency along with their clinical, biochemical and molecular data. The age at diagnosis of our patients ranges from 0 to 14 years. The age of onset of seizures usually ranges from infancy to 3 years. However, one of our patients developed seizures at age 5; progressing to myoclonic epilepsy at age 8 years and another patient has not developed seizures at age 17 years. Five novel mutations were identified: c.37ins26 (p.G13PfsX38), c.403G>T (p.D135Y), c.507&#95;521dup15 (p.C169&#95;S173dup), c.402C>G (p.Y134X) and c.610&#95;611delAGinsGAA (p.R204EfsX63). Six patients had the c.327G>A (last nucleotide of exon 2) splice-site mutation which suggests that this is one of the most common mutations in the GAMT gene, second only to the known Portuguese founder mutation, c.59G>C (p.W20S). Our data suggests that the clinical presentation can be variable and the diagnosis may be overlooked due to unawareness of this disorder. Therefore, GAMT deficiency should be considered in the differential diagnosis of progressive myoclonic epilepsy as well as in unexplained developmental delay or regression with dystonia, even if the patient has no history of seizures. As more patients are reported, the prevalence of GAMT deficiency will become known and guidelines for prenatal diagnosis, newborn screening, presymptomatic testing and treatment, will need to be formulated.