Microcephaly, disproportionate pontine, and cerebellar hypoplasia syndrome: Two novel mutations in the CASK gene were discovered in Chinese females.

Microcephaly, disproportionate pontine and cerebellar hypoplasia (MICPCH) syndrome is a rare and genetic disorder, which is mainly caused by mutations in the CASK gene. We described four variations in the CASK gene in Chinese female patients with MICPCH, who presented with microcephaly, developmental delay, and motor disorder. The CASK mutations were identified using NGS (the next-generation sequencing), copy number variation sequencing. Two novel variations in the CASK gene were revealed including a frameshift mutation c.1000_1001insG (p.Asp334GlyfsTer32) and a nonsense mutation c.2110A > T (p.Lys704Ter). Two other aberrations were c.316C > T (p.Arg106Ter) and Xp11.4-p11.3 (41,700,001-44,660,000) × 1 loss. We provided clinical manifestations and neuroimaging findings of the four patients. The genetic variation spectrum of MICPCH caused by CASK was updated. Furthermore, we expounded on the molecular mechanism of the disease and noticed that it was not possible to relate the magnitude of the genetic alteration to a particular phenotype.