Postmortem Diagnostic Exome Sequencing Identifies a De Novo TUBB3 Alteration in a Newborn With Prenatally Diagnosed Hydrocephalus and Suspected Walker

Abstract

Objective

Herein, we report a case of a deceased newborn with prenatally detected hydrocephalus. Postnatal findings included abnormal brain imaging and electroencephalogram, 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 postmortem case after traditional testing methods were uninformative. The DES results allowed for reproductive options, such as preimplantation genetic diagnosis and/or prenatal diagnosis, to be available to the parents in future pregnancies.

Keywords

TUBB3 protein human exome clinical diagnostic sequencing postmortem diagnosis Walker–Warburg syndrome abnormal brain hydrocephalus

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Postmortem Diagnostic Exome Sequencing Identifies a De Novo TUBB3 Alteration in a Newborn With Prenatally Diagnosed Hydrocephalus and Suspected Walker–Warburg Syndrome

Abstract

Objective

Methods

Results

Conclusion

Keywords

Get full access to this article

References

Supplementary Material