Purpose: Our work is the first documentation, in real time, of workflow in a general genetics department including data on patient care, research, and other activities for both clinical geneticists and genetic counselors. Methods:All physician geneticists and genetic counselors in the medical genetics department used an electronic tool to record their activities in 15 minute increments during clinic hours, evenings, and weekends over a 10-week period.Results: The average work week was 54.1 hours for physicians and 43.5 hours for genetic counselors. During clinic hours physicians spent about one-fourth of their time on direct patient care, one-fourth on other patient-related activities, one-fourth on research unrelated to individual patient care, and the remaining fourth on all other activities. However, after hours and on weekends they spent most of their time on research. Genetic counselors spent half of their time on patient-related activities, one-fourth on direct patient care, and the remainder on all other activities. The total professional time averaged 7 hours per new patient and 3.5 hours per follow-up with nearly 60% of this time devoted to patient-related activities. Conclusions: The labor intensive nature of clinical genetics, the large amount of time devoted to patient-related activities, and continuing limitations on billing by genetic counselors all contribute to the financial challenges faced by genetics departments. Genet Med 2008:10(9):699 -706. Key Words: clinical genetics services, workforce, workflow, time study, reimbursement, genetic counselingProvision of medical genetics services is a time and labor intensive activity. 1,2 The detailed three generation pedigree not only takes far longer than the standard family history screening in primary care (which adds an average of only 3 min to a primary care visit 3 ), but frequently must be supplemented by acquisition and review of medical records of affected relatives, examination of parents and other relatives (who don't usually have their own appointments), and the review of family photographs when affected relatives are unavailable. Because of the complexity of modern genetic knowledge and the need to discuss implications for multiple family members, face-to-face genetic counseling is time-consuming. The ordering, insurance preauthorization, and follow-up of increasingly complex laboratory tests, literature review for rare diagnoses, and documentation of the visit (which is more extensive than in most disciplines due to the need to educate referring providers about rare disorders), as well as writing and reviewing of detailed summary letters for the family also contribute to the work of genetic counseling. Although some of these challenges exist in other fields, genetics remains unique in terms of dependence on family information. Furthermore, because most genetic disorders are rare, time savings through standardization of protocols, documentation tools, and patient education materials are rarely applicable. Rapid advances in genetic knowledge...

Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein (LDL) cholesterol and premature cardiovascular disease, with a prevalence of approximately 1 in 200-500 for heterozygotes in North America and Europe. Monogenic FH is largely attributed to mutations in the LDLR, APOB, and PCSK9 genes. Differential diagnosis is critical to distinguish FH from conditions with phenotypically similar presentations to ensure appropriate therapeutic management and genetic counseling. Accurate diagnosis requires careful phenotyping based on clinical and biochemical presentation, validated by genetic testing. Recent investigations to discover additional genetic loci associated with extreme hypercholesterolemia using known FH families and population studies have met with limited success. Here, we provide a brief overview of the genetic determinants, differential diagnosis, genetic testing, and counseling of FH genetics.

Award Number: WT098051 DDX3X (Xp11.4) encodes a DEAD-box RNA helicase that escapes X chromosome inactivation.Pathogenic variants in DDX3X have been shown to cause X-linked intellectual disability (ID) (MRX102, MIM: 300958). The phenotypes associated with DDX3X variants are heterogeneous and include brain and behavioral abnormalities, microcephaly, hypotonia, and movement disorders and/or spasticity. The majority of DDX3X variants described are de novo mutations in females with ID. In contrast, most male DDX3X variants are inherited from an unaffected mother, with one documented exception being a recently identified de novo splice site variant.It has been suggested, therefore, that DDX3X exerts its effects through haploinsufficiency in females, and that affected males carry hypomorphic alleles that retain partial function. Given the lack of male de novo DDX3X variants, loss-of-function variants in this gene are suspected to be male lethal. Through whole-exome sequencing, we identified three unrelated males with hemizygous missense DDX3X variants and ID. All three variants were confirmed by Sanger sequencing, with two established as de novo. In silico analyses were supportive of pathogenicity. We report the male phenotypes and compare them to phenotypes observed in previously reported male and female patients. In conclusion, we propose that de novo DDX3X variants are not necessarily male lethal and should be considered as a cause of syndromic ID in both males and females.

There has been one previous report of a cohort of patients with variants in Chromodomain Helicase DNA-binding 3 ( CHD3 ), now recognized as Snijders Blok-Campeau syndrome. However, with only three previously-reported patients with variants outside the ATPase/helicase domain, it was unclear if variants outside of this domain caused a clinically similar phenotype. We have analyzed 24 new patients with CHD3 variants, including nine outside the ATPase/helicase domain. All patients were detected with unbiased molecular genetic methods. There is not a significant difference in the clinical or facial features of patients with variants in or outside this domain. These additional patients further expand the clinical and molecular data associated with CHD3 variants. Importantly we conclude that there is not a significant difference in the phenotypic features of patients with various molecular disruptions, including whole gene deletions and duplications, and missense variants outside the ATPase/helicase domain. This data will aid both clinical geneticists and molecular geneticists in the diagnosis of this emerging syndrome.