Post Mortem Diagnostic Exome Sequencing Identifies a de novo TUBB3 Alteration in a Newborn with Prenatally Diagnosed Hydrocephalus and Suspected Walker-Warburg Syndrome.

OBJECTIVE: Herein we report a case of a deceased newborn with prenatally detected hydrocephalus. Postnatal findings included abnormal brain imaging and electroencephalogram (EEG), optic nerve abnormalities, and elevated creatine kinase (CK). No underlying genetic etiology had been previously identified for the proband, despite testing with a congenital muscular dystrophy gene panel. METHODS: Diagnostic exome sequencing (DES) was performed on the proband-parents trio, and candidate alterations were confirmed using automated fluorescence dideoxy sequencing. RESULTS: Exome sequencing of the proband, mother and father identified a previously unreported apparently de novo heterozygous tubulin, beta-3 (TUBB3) c.523G>C (p.V175L) alteration in the proband. CONCLUSION: Overall, DES established a likely molecular genetic diagnosis for a post-mortem case after traditional testing methods were uninformative. The DES results allowed for reproductive options, such as preimplantation genetic diagnosis (PGD) and/or prenatal diagnosis, to be available to the parents in future pregnancies.

• Authors: Zöe Powis; Adam C. Chamberlin; Christina Alamillo; Ceulemans S; Lynne M. Bird; Sha Tang
• Journal: Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
• Date: 2017 - Aug