Generation and characterization of an iPSC line (SHCMDLi001-A) from a 12-year-old Chinese Han patient with TRAF7 syndrome and of an iPSC line (SHCMDLi002-A) from a control individual.

Mutations in TRAF7 cause developmental delay and cardiac, facial, digital anomalies. c.1964G > A variant was most recurrent, suggesting its essentiality of pathogenicity. Further studies to determine the underlying mechanism of c.1964G > A variant are warranted. But no patient-specific cellular models have been generated. Here, we generated an iPSC line with c.1964G > A variant (SHCMDLi001-A) and a line from healthy individual (SHCMDLi002-A). Characterization of SHCMDLi001-A and SHCMDLi002-A demonstrated these iPSCs are free of exogenous reprogramming genes, expressed pluripotency markers, exhibited a normal karyotype and were potential of three germ layer differentiation. These lines provide a valuable resource for studying disease-causing mechanism of TRAF7 variant.

A de novo MAPRE2 variant in a patient with congenital symmetric circumferential skin creases type 2.

BACKGROUND: Congenital symmetric circumferential skin creases (CSCSC) was initially described five decades ago. Exome sequencing has recently revealed the genetic etiology of CSCSC. Pathogenic variants in TUBB (OMIM# 191130) and MAPRE2 (OMIM# 605789) have been linked to CSCSC1 (OMIM# 156610) and CSCSC2 (OMIM# 616734), respectively, in an autosomal dominant manner. Four pathogenic variants in MAPRE2 have been previously reported to be associated with CSCSC2. METHODS: Whole-exome sequencing (WES) has been performed and an in-house pipeline was used to conduct a phenotype-driven data analysis. All candidate variants were confirmed by Sanger sequencing. RESULTS: Here we report a 2-year-old boy characterized by absent expressive speech, normal to mild over growth, facial dysmorphic features, remarkable circumferential skin creases on both forearms and ankles. WES disclosed a de novo missense MAPRE2 variant, c.518G>A (p.Arg173Gln), as the molecular cause of this complex phenotype. We described detailed clinical characterization of this patient and compared the available clinical data of individuals with MAPRE2 variants to demonstrate the phenotypic spectrum. CONCLUSION: Our study reports the first patient of Asian origin with CSCSC2 due to a pathogenic mutation of MAPRE2 and expands the clinical and genetic spectrum of CSCSC2.

Expression characteristic and significance of interleukin-6, nuclear factor kappa beta, and bone formation markers in rat models of osteoporosis.

The goal of this study was to investigate the expression levels of interleukin 6 (IL-6), nuclear factor kappa beta (NF-kappabeta), bone-specific alkaline phosphatase (BALP), and bone osteocalcin (BGP) in rats with osteoporosis and their significance in the pathogenesis of osteoporosis. In all, 60 adult female SD rats were divided randomly into 3 groups of 20 rats each: normal control group (control), sham-operated group (sham), and ovariectomized group (OVX). In 2, 3, 4, 5, and 6 months after surgery, 4 rats were randomized from each group for assays of BMD, IL-6, BALP, and BGP. Then, the rats were sacrificed for the detection of IL-6 and NF-kappabeta expression levels in bone tissue by quantitative real-time RT-PCR analysis. Compared with the sham (0.097 +/- 0.04 g/cm2, 0.097 +/- 0.01 g/cm2, 0.095 +/- 0.07 g/cm2) and control group (0.107 +/- 0.01 g/cm2, 0.103 +/- 0.07 g/cm2, 0.108 +/- 0.06 g/cm2), the BMD of rats in the OVX group was reduced remarkably in 4, 5, and 6 months (0.082 +/- 0.05 g/cm2, 0.073 +/- 0.02 g/cm2, 0.061 +/- 0.05 g/cm2, respectively; P < 0.01); the serum IL-6 level increased significantly from 2 to 6 months after surgery (P < 0.01); and the serum levels of BALP and BGP were greater at 4, 5, and 6 months (P < 0.05). The quantitative real-time RT-PCR analysis demonstrated that IL-6 and NF-kappabeta mRNA levels in OVX group increased in a time-dependent manner. Moreover, the IL-6, NF-kappabeta, BALP, and BGP levels were correlated negatively with the BMD. Meanwhile, a positive correlation was observed between IL-6 and NF-kappabeta. In conclusion, the expression levels of IL-6, NF-kappabeta, and bone formation markers may increase significantly in the osteoporosis rats. These molecules could play a role in the pathogenesis.