Findings demonstrate the breadth of disease severity in CACNA1A-related disease and suggest that the clinical phenotypic heterogeneity likely reflects diverse molecular phenotypes.

A single origin of GJB2 c.235delC allele and multiple, independent origin of c.109G > A allele in Chinese non-syndromic hearing loss population.

We demonstrate through molecular genetic studies that a novel human neurological syndrome is caused by bi-allelic variant in PSMC1, encoding a component of the base unit of the eukaryotic proteasome. Our functional studies in fruit flies validate pathogenicity of the variant: phenotypic effects of abrogation of the PSMC1 Drosophila ortholog (Rpt2) were fully reversed through complementation studies with the wild-type human PSMC1 yet not with the mutant PSMC1.

Mutations in LRP5 are associated with dental anomalies. We also show for the first time that mutations in BMP4 are implicated in root maldevelopment and torus mandibularis. Sharing of the phenotypes of the patients with LRP5 and BMP4 mutations implicates cross talks between WNT/β-catenin and BMP signaling pathways, especially during root development.

A novel variation c.486-1G>A in POPDC3 was found in a Chinese Limb-Girdle muscular dystrophy pedigree. The variation alters the splicing form of POPDC3, truncates the protein encoded by this gene and causes disease.

We report a 19-month-old patient with cardiomyopathy as the first presenting feature of primary COQ10 deficiency-6. This case expands the phenotypic spectrum of this disorder. Furthermore, it shows that genetic testing for primary COQ10 deficiency should be considered in patients with pediatric-onset cardiomyopathy as it can guide treatment options.

(A) Sanger sequencing confirmation and family pedigree for the patient. (B) A schematic representation of transcript and translation showing the positions of all CAPZA2 variants identified.