Utilization of telehealth in paediatric genome-wide sequencing: Health services implementation issues in the CAUSES Study.

INTRODUCTION: Genome-wide sequencing (exome or whole genome) is transforming the care and management of paediatric patients with a rare disease because of its diagnostic capabilities. Genome-wide sequencing is most effective when both parents and the child are sequenced as a trio. Genetic counselling is recommended for all families considering genome-wide sequencing. Although telehealth is well established in genetic counselling for hereditary cancer and prenatal genetics, its use with genome-wide sequencing has not been well studied. The CAUSES Clinic at BC Children's and Women's Hospitals was a translational paediatric trio-based genome-wide sequencing initiative. Pre-test genetic counselling via telehealth (at a clinical site near the family's residence) was offered to families who had been previously evaluated by a clinical geneticist. We report on the first 300 families seen in the CAUSES clinic and compare health services implementation issues of families seen via telehealth versus on-site. METHODS: Demographics, cost to families (travel and time), time to first appointment, complete trio sample accrual and diagnostic rates were studied. RESULTS: Of the 300 patients, 58 (19%) were seen via telehealth and 242 (81%) were seen on-site for pre-test counselling. The mean time to completion of accrual of trio samples in the telehealth group was 56.3 (standard deviation ±87.3) days versus 18.9 (standard deviation ±62.4) days in the onsite group (p < 2.2 × 10-16). The mean per-family estimated actual or potential travel/time cost savings were greater in the telehealth group (Can$987; standard deviation = Can$1151) than for those seen on-site (Can$305; standard deviation = Can$589) (p = 0.0004). CONCLUSIONS: Telehealth allowed for access to genome-wide sequencing for families in remote communities and for them to avoid significant travel and time costs; however, there was a significant delay to accrual of the complete trio samples in the telehealth group, impacting on time of result reporting and delaying diagnoses for families for whom genome-wide sequencing was diagnostic.

Expression profile of NSDHL in human peripheral tissues.

NAD(P) steroid dehydrogenase-like (NSDHL) is an X-linked gene that encodes a 3ß-hydroxysteroid dehydrogenase in the cholesterol biosynthetic pathway. Loss-of-function mutations in NSDHL cause Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects (CHILD) and CK syndromes. CHILD syndrome is a male lethal X-linked dominant disorder characterized by asymmetric skin and limb anomalies in affected females. CK syndrome is an intellectual disability disorder characterized by disproportionate short stature, brain malformations, and dysmorphic features in affected males. To understand better the relationship of the expression of mRNA and protein encoded by human NSDHL to the peripheral malformations of these disorders, we characterized the peripheral expression of the mRNA and protein by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), immunoblotting and immunohistochemistry. We also profiled the mRNA expression of mouse Nsdhl by in situ hybridization. Expression of the mRNA and protein encoded by human NSDHL parallels that of mouse Nsdhl mRNA for most but not all tissues. Furthermore, human NSDHL protein and mouse Nsdhl mRNA were expressed in tissues synthesizing cholesterol and steroids and in all peripheral tissues affected by CHILD or CK syndromes.