Mutant CARD10 in a family with progressive immunodeficiency and autoimmunity

Autoimmunity and immunodeficiency were previously considered to be mutually exclusive conditions.However,an increased understanding of the complex immune regulatory systems and signaling mechanisms,coupled with the application of genetic analysis,has demonstrated the complex relationships between the two kinds of diseases.1 In recent years,several mild forms of primary immunodeficiencies have been discovered,presenting with opportunistic infections overlapping autoimmunity and/or allergy late in life.

A novel variant in TBX20 （p.DI76N） identified by whole-exome sequencing in combination with a congenital heart disease related gene filter is associated with familial atrial septal defect

Congenital heart disease （CHD） is the leading cause of birth defects, and its etiology is not completely understood. Atrial septal defect （ASD） is one of the most common defects of CHD. Previous studies have demonstrated that mutations in the transcription factor T-box 20 （TBX20） contribute to congenital ASD. Whole-exome sequencing in combination with a CHD-related gene filter was used to detect a family of three generations with ASD. A novel TBX20 mutation, c.526G〉A （p.D176N）, was identified and co-segregated in all affected members in this family. This mutation was predicted to be deleterious by bioinformatics programs （SIFT, Polyphen2, and MutationTaster）. This mutation was also not presented in the current Single Nucleotide Polymorphism Database （dbSNP） or National Heart, Lung, and Blood Institute （NHLBI） Exome Sequencing Project （ESP）. In conclusion, our finding expands the spectrum of TBX20 mutations and provides additional support that TBX20 plays important roles in cardiac development. Our study also provided a new and cost-effective analysis strategy for the genetic study in small CHD pedigree.

Haploinsufficiency of syncoilin leads to hypertrophic cardiomyopathy

Here we reported a SYNC nonsense variant in a Chinese family with hypertrophic cardiomyopathy(HCM)and firstly linked syncoilin(SYNC)to HCM.HCM is an inherited cardiovascular disease,affecting approximately 1:500 people,that is characterized by thickening of left ventricle(LV),especially the interventricular septum(IVS),and diastolic ventricular failure.1 To date,more than 15 genes of two groups underlying HCM have been identified.1 About 35%e60%HCM patients present autosomal dominant inheritance and carry a pathogenic variant in sarcomeric protein genes,such as b-myosin heavy chain(MYH7),myosin binding protein C(MYBPC3),and Troponin T(TNNT2).1 In addition,non-sarcomeric genetic causes of disease have also been observed in about 25%HCM patients,mainly related to metabolic storage diseases,mitochondrial cardiomyopathies,inborn errors of metabolism etc.