Case report: a novel mutation in ZIC2 in an infant with microcephaly, holoprosencephaly, and arachnoid cyst.

RATIONALE: Holoprosencephaly (HPE) is a severe congenital brain malformation resulting from failed or incomplete forebrain division in early pregnancy.

PATIENT CONCERNS: In this study, we reported a 9-month old infant girl with mild microcephaly, semilobor HPE, and arachnoid cyst.

DIAGNOSES: Potential genetic defects were screened directly using trio-case whole exome sequencing (WES) rather than traditional karyotype, microarray, and Sanger sequencing of select genes.

OUTCOMES: A previous unpublished de novo missense mutation (c.1069C >G, p.H357D) in the 3rd zinc finger domain (ZFD3) of the ZIC2 gene was identified in the affected individual, but not in the parents. Sanger sequencing using specific primers verified the mutation. Extensive bioinformatics analysis confirmed the pathogenicity of this extremely rare mutation. Phenotype-genotype analysis revealed significant correlation between the 3rd zinc-finger domain with semilobor HPE.

LESSONS: These findings expanded the spectrum of the ZIC2 gene mutations and associated clinical manifestations, which is the first identification of a mutated ZIC2 gene in a Han infant girl with mild microcephaly, semilobor HPE, and arachnoid cyst.