A case of TBC1D32-related ciliopathy with novel compound heterozygous variants

Primary cilium has a signal transduction function that is essential for brain development, and also determines cell polarity and acts as a mediator for important signaling systems, especially the Sonic Hedgehog (SHH) pathway. TBC1D32 is a ciliary protein, implicated in SHH signaling. Biallelic mutations in the TBC1D32 gene causes a kind of ciliopathy, heterogeneous developmental or degenerative disorders that affect multiple organs, including the brain. Here we report a boy who carried compound heterozygous variants in TBC1D32. The patient showed hypotonia, respiratory difficulty, and multiple anomalies at his birth. He was diagnosed with congenital hypopituitarism and treated with T4, hydrocortisone, and growth hormone. Despite the hormonal replacement, the patient needed long-term respiratory support with tracheostomy and nutritional support with a feeding tube. His developmental milestones were severely retarded. Hydrocephalus and strabismus developed and both required surgery, during the outpatient follow-up. Whole-exome sequencing indicated compound heterozygous variants, c.2200C>T (p.Arg734*) and c.156-1G>T, in TBC1D32 gene. This is the first Korean case of TBC1D32-related ciliopathy and we reported detailed and sequential clinical features. This case demonstrated the utility of whole-exome sequencing and provided valuable clinical data on ultra-rare disease.

A case of TBC1D32-related ciliopathy with novel compound heterozygous variants

Primary cilium has a signal transduction function that is essential for brain development, and also determines cell polarity and acts as a mediator for important signaling systems, especially the Sonic Hedgehog (SHH) pathway. TBC1D32 is a ciliary protein, implicated in SHH signaling. Biallelic mutations in the TBC1D32 gene causes a kind of ciliopathy, heterogeneous developmental or degenerative disorders that affect multiple organs, including the brain. Here we report a boy who carried compound heterozygous variants in TBC1D32. The patient showed hypotonia, respiratory difficulty, and multiple anomalies at his birth. He was diagnosed with congenital hypopituitarism and treated with T4, hydrocortisone, and growth hormone. Despite the hormonal replacement, the patient needed long-term respiratory support with tracheostomy and nutritional support with a feeding tube. His developmental milestones were severely retarded. Hydrocephalus and strabismus developed and both required surgery, during the outpatient follow-up. Whole-exome sequencing indicated compound heterozygous variants, c.2200C>T (p.Arg734*) and c.156-1G>T, in TBC1D32 gene. This is the first Korean case of TBC1D32-related ciliopathy and we reported detailed and sequential clinical features. This case demonstrated the utility of whole-exome sequencing and provided valuable clinical data on ultra-rare disease.

A Case of Neonatal Cerebral Infarction associated with Mutation in homozygous MTHFR C677T Gene / 대한주산의학회잡지

C677T mutation in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) predisposes to hyperhomocysteinemia in vivo and is known to be one of the causes of perinatal ischemic stroke. As MTHFR plays a role in the metabolism of homocysteine, C677T mutation may account for reduced enzymatic activity resulting in hyperhomocysteinemia. This may be prevented by introducing activity-enhancing coenzymes such as folic acid, vitamin B6, and B12. Though C677T mutation is known as a significant risk factor for cerebral infarction, reported cases of cerebral infarction among affected neonates are scarce. This report describes a case of a neonate homozygous for C677T mutation who had a perinatal ischemic stroke, born in a mother whose folic acid and nutritional consumption had been reduced during pregnancy.

Proteomic analysis of domestic pig pancreas during development using two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry / 한국실험동물학회지

Pig pancreas may be a therapeutic resource for human diabetic patients. However, this potential is hindered by a lack of knowledge of the molecular events of pig pancreas development. In this study, the embryonic day 60, neonate and 6-month protein profiles of pig pancreas were ascertained at using two-dimensional gel electrophoresis and matrix assisted laser desorption/ionization-time of flight mass spectrometry. Twenty four proteins were differentially expressed during pig pancreas development. Among them, 12 spots increased and 7 spots decreased according to development. The expression of 5 protein were highest at birth. Expression of digestive enzymes including trypsin, pancreatic triacylglycerol lipase and pancreatic alpha-amylase was elevated in adults, whereas chymotrypsins were highly expressed in neonates. Proteins that were abundantly expressed during gestation were alpha-1-antitrypsin, alpha-fetoprotein and transferrins. Taken together, we found out that several proteins were significantly up- or down- regulated from pig pancreas based on developmental stage. This study will provide basis for understanding development of pig pancreas.

Comparison of Invariant NKT Cells with Conventional T Cells by Using Gene Set Enrichment Analysis (GSEA)

BACKGROUND: Invariant Natural killer T (iNKT) cells, a distinct subset of CD1d-restricted T cells with invariant Valphabeta TCR, functionally bridge innate and adaptive immunity. While iNKT cells share features with conventional T cells in some functional aspects, they simultaneously produce large amount of Th1 and Th2 cytokines upon T-cell receptor (TCR) ligation. However, gene expression pattern in two types of cells has not been well characterized. METHODS: we performed comparative microarray analyses of gene expression in murine iNKT cells and conventional CD4+CD25-gammadeltaTCR- T cells by using Gene Set Enrichment Analysis (GSEA) method. RESULTS: Here, we describe profound differences in gene expression pattern between iNKT cells and conventional CD4+CD25-gammadeltaTCR- T cells. CONCLUSION: Our results provide new insights into the functional competence of iNKT cells and a better understanding of their various roles during immune responses.