Transferring Exome Sequencing Data from Clinical Laboratories to Healthcare Providers: Lessons Learned at a Pediatric Hospital.

The adoption rate of genome sequencing for clinical diagnostics has been steadily increasing leading to the possibility of improvement in diagnostic yields. Although laboratories generate a summary clinical report, sharing raw genomic data with healthcare providers is equally important, both for secondary research studies as well as for a deeper analysis of the data itself, as seen by the efforts from organizations such as American College of Medical Genetics and Genomics and Global Alliance for Genomics and Health. Here, we aim to describe the existing protocol of genomic data sharing between a certified clinical laboratory and a healthcare provider and highlight some of the lessons learned. This study tracked and subsequently evaluated the data transfer workflow for 19 patients, all of whom consented to be part of this research study and visited the genetics clinic at a tertiary pediatric hospital between April 2016 to December 2016. Two of the most noticeable elements observed through this study are the manual validation steps and the discrepancies in patient identifiers used by a clinical lab vs. healthcare provider. Both of these add complexity to the transfer process as well as make it more susceptible to errors. The results from this study highlight some of the critical changes that need to be made in order to improve genomic data sharing workflows between healthcare providers and clinical sequencing laboratories.

Integrating a Geneticist in a Multidisciplinary Clinic for Down Syndrome Increases Commitment to Genetic Counseling.

BACKGROUND: Although most physicians and genetic professionals are familiar with Down syndrome, many families do not have experience with Down syndrome before having a child diagnosed. The American Academy of Pediatrics has specific recommendations for genetic counseling and chromosome analysis for Down syndrome. LOCAL PROBLEM: The literature indicates that adherence to completion of appropriately timed genetic counseling is low at 31%. This study was initiated to determine our adherence rates and to improve if needed. METHODS: In the Down syndrome clinic at Nationwide Children's Hospital, a subspecialty clinic in the Division of Developmental and Behavioral Pediatrics, a genetic counselor was on-call but did not routinely attend. The intervention consisted of multidisciplinary care with the presence of a clinical geneticist. Statistical Process Control Charts and Fisher's exact test were used to determine the impact of the intervention. RESULTS: Our baseline rate of adherence to genetic counseling was similar to previous publications. Direct genetics involvement in the Down syndrome clinic in place of an on-call genetic counselor led to significant improvement in adherence to genetic counseling recommendations over a 6-month period from 35% to 62%, P < 0.001 and sustained for 6 months. Postclinic adherence rates and subanalyses by age showed similar results. The final postvisit adherence rate of 89% in February 2017 demonstrates continued improvement. Geneticist involvement allowed chromosome reports uploading and karyotype listing in electronic medical records. IMPLICATIONS AND LESSONS LEARNED: Genetic counseling in newborns with Down syndrome is important, yet was often not received at Nationwide Children's Hospital before this study. Integrating a geneticist resulted in improvement. Implementing similar models at other institutions can ensure that the correct genetic testing is completed, results documented and families counseled appropriately.

Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis.

Neonatal cholestasis is a potentially life-threatening condition requiring prompt diagnosis. Mutations in several different genes can cause progressive familial intrahepatic cholestasis, but known genes cannot account for all familial cases. Here we report four individuals from two unrelated families with neonatal cholestasis and mutations in NR1H4, which encodes the farnesoid X receptor (FXR), a bile acid-activated nuclear hormone receptor that regulates bile acid metabolism. Clinical features of severe, persistent NR1H4-related cholestasis include neonatal onset with rapid progression to end-stage liver disease, vitamin K-independent coagulopathy, low-to-normal serum gamma-glutamyl transferase activity, elevated serum alpha-fetoprotein and undetectable liver bile salt export pump (ABCB11) expression. Our findings demonstrate a pivotal function for FXR in bile acid homeostasis and liver protection.