A case of early-onset spinocerebellar ataxia type 5 / 中华神经科杂志

Spinocerebellar ataxias are a high clinically and genetically heterogeneous group of neurodegenerative disorders, usually belongs to autosomal dominant hereditary cerebellar ataxia. Spinocerebellar ataxia type 5 (SCA5) is one of the extremely rare subtypes and caused by heterozygous mutation of SPTBN2 gene. A case of infant-onset SCA5 patient is reported, mainly manifested as global developmental delay, ataxia and dysarthria, carrying the heterozygous missense variant c.1438C>T (p. Arg480Trp) in the SPTBN2 gene. This mutation may have an important impact on functional regions of the β-Ⅲ spectrin, leading to the occurrence of disease.

Expression and clinical application of SPTBN1 in nasopharyngeal carcinoma / 中华检验医学杂志

Objective@#The expression of spectrin beta chain, brain1(SPTBN1) were measured in nasopharyngeal carcinoma (NPC) cell lines, as well as tissues and serums of NPC cases and normal controls. The clinical value of SPTBN1 expression for NPC diagnosis were assessed along with the antibody levels of early antigen-IgA(EA-IgA) and viral capsid antigen-IgA(VCA-IgA).@*Methods@#A total of 71 nasopharynx tissue specimens and 130 serum from both NPC cases and matched health controls were collected from December 2016 to December 2018. In logistic regression the levels of SPTBN1, EA-IgA, VCA-IgA were identified and included in an integrative risk prediction model. Discriminatory accuracy was measured by generation of receiver operator curves and estimation of area under the curve (AUC).@*Results@#The SPTBN1 concentration in cell lines from NP69, 6-10B to 5-8F showed a decreasing trend (H=50.205, P<0.05). The SPTBN1 expression level in serums were significantly lower [73(42, 142)] compared to controls, while EA-IgA and VCA-IgA levels [3.42(1.29, 5.19),3.55(1.95, 5.01)]were higher in NPC serum samples (HSPTBN1=24.105, HEA-IgA=52.398, HVCA-IgA=70.426, P<0.01). The findings were confirmed in tissues that the positive SPTBN1 rate were significantly lower in cases (86.7%) as compared to controls (43.9%, χ2=13.443, P<0.001). In the risk prediction model for NPC diagnosis, the AUC of SPTBN1 alone and the integrated regression model were 0.794 and 0.987, respectively (Z=4.900,P<0.01).@*Conclusions@#The lower expression of SPTBN1 was a potential marker in NPC diagnosis. The combined analysis of SPTBN1, EA-IgA and VCA-IgA may improve the sensitivity and specificity in NPC diagnosis.

Expression and clinical application of SPTBN1 in nasopharyngeal carcinoma / 中华检验医学杂志

Objective The expression of spectrin beta chain, brain1(SPTBN1) were measured in nasopharyngeal carcinoma (NPC) cell lines, as well as tissues and serums of NPC cases and normal controls. The clinical value of SPTBN1 expression for NPC diagnosis were assessed along with the antibody levels of early antigen-IgA(EA-IgA) and viral capsid antigen-IgA(VCA-IgA). Methods A total of 71 nasopharynx tissue specimens and 130 serum from both NPC cases and matched health controls were collected from December 2016 to December 2018. In logistic regression the levels of SPTBN1, EA-IgA, VCA-IgA were identified and included in an integrative risk prediction model. Discriminatory accuracy was measured by generation of receiver operator curves and estimation of area under the curve (AUC). Results The SPTBN1 concentration in cell lines from NP69, 6-10B to 5-8F showed a decreasing trend (H=50.205, P<0.05). The SPTBN1 expression level in serums were significantly lower [73(42, 142)] compared to controls, while EA-IgA and VCA-IgA levels [3.42(1.29, 5.19), 3.55(1.95, 5.01)]were higher in NPC serum samples (HSPTBN1=24.105, HEA-IgA=52.398, HVCA-IgA=70.426, P<0.01). The findings were confirmed in tissues that the positive SPTBN1 rate were significantly lower in cases (86.7％) as compared to controls (43.9％,χ2=13.443, P<0.001). In the risk prediction model for NPC diagnosis, the AUC of SPTBN1 alone and the integrated regression model were 0.794 and 0.987, respectively (Z=4.900,P<0.01).Conclusions The lower expression of SPTBN1 was a potential marker in NPC diagnosis. The combined analysis of SPTBN1, EA-IgA and VCA-IgA may improve the sensitivity and specificity in NPC diagnosis.

Hereditary polycythemia caused by mutation of ANK1 gene:a case report / 临床儿科杂志

Objective To explore the genetic characteristics, diagnosis, and treatment of hereditary spherical polycythemia (HS). Methods The clinical data of one case of HS was analyzed retrospectively, and related literatures were reviewed. Results The 5-year-old girl presented hemolytic anemia from 6 months old. Incubation of fragility tests was positive. Blood smears and red cell electron microscopy showed spherical red blood cells. DNA sequencing showed alterations in heterozygosity of stopgain SNV. The girl was diagnosed was HS, and was scheduled to undergo splenectomy at 6 years old. Conclusions HS is an autosomal dominant genetic disease, mainly manifested as anemia, hemolytic anemia, and splenomegaly. The early diagnosis depends on genetic testing.

Investigation on the interaction of human testis protein SPAG4L with KASH domain protein Nesprin-3 / 临床检验杂志

Objective To investigate the interaction of human testis sperm-associated antigen 4 like(SPAG4L) protein containing Sad,UNC-84(SUN) domain with nuclear envelop spectrin repeat proteins 3 (Nesprin-3) containing Klarsicht,ANC-1 and Syne homology (KASH) domain.Methods SPAC-4L protein domains were analyzed with the bioinformatics method.After the SPAG4L plasmid was transfected into Ntera-2 cells,the subcellular localization of SPAG4L was observed.The interaction of SPAG4L with Nesprin-3 was determined by immunofluorescence,co-immunoprecipitation(co-IP) and bimolecular fluorescence complementation (BiFC) technology,respectively.Results Bioinformatics analysis results showed that there was a transmembrane structure in SPAG4L protein.Subcellular localization results demonstrated that SPAG4L protein located in the nuclear membrane and cytoplasm.Immunofluorescence,Co-IP,and BiFC results showed that there was an interaction between SPAG4L and Nesprin-3,and that a LINC(linkers of the nucleoskeleton to the cytoskeletan) complex was formed.Conclusion SPAG4L may interact with Nesprin-3 to form a LINC complex,which is important for understanding the function of SPAG4L protein in spermatogenesis.

A Patient Diagnosed with Spinocerebellar Ataxia Type 5 associated with SPTBN2: Case Report / 대한소아신경학회지

Spinocerebellar ataxias (SCAs) are autosomal dominant neurodegenerative disorders which disrupt the afferent and efferent pathways of the cerebellum that cause cerebellar ataxia. Spectrin beta non-erythrocytic 2 (SPTBN2) gene encodes the β-III spectrin protein with high expression in Purkinje cells that is involved in excitatory glutamate signaling through stabilization of the glutamate transporter, and its mutation is known to cause spinocerebellar ataxia type 5. Three years and 5 months old boy with delayed development showed leukodystrophy and cerebellar atrophy in brain magnetic resonance imaging (MRI). Diagnostic exome sequencing revealed that the patient has heterozygous mutation in SPTBN2 (p.Glu1251Gln) which is a causative genetic mutation for spinocerebellar ataxia type 5. With the patient's clinical findings, it seems reasonable to conclude that p.Glu1251Gln mutation of SPTBN2 gene caused spinocerebellar ataxia type 5 in this patient.

Spectrin Cleavage Induced by LLP-1 Lentivirus Lytic Peptide Domain in the Intracytoplasmic Tail of Human Immunodeficiency Virus Type 1 GP41 in Rat Organotypic Hippocampal Slice Cultures

We previously demonstrated that the lentivirus lytic peptide 1 (LLP-1) corresponding to the carboxyl terminus of HIV-1 gp41 induced cell death in human neuronal cells. Present study was conducted to further elucidate the pathogenic mechanisms involved in HIV-1 gp41-induced neurodegeneration in AIDS patients with cognitive deficits. The effect of LLP-1 on activation of calpain-1, a calcium-activated cysteine protease, which has been implicated in neuronal degeneration and death, was monitored by the proteolysis of spectrin in rat organotypic hippocampal slice cultures. Protease specific spectrin breakdown products revealed that LLP-1 generated~150/145-kDa fragments characteristic of calpain-1 activation in hippocampus undergoing cell death as evidenced by LDH release. This spectrin cleavage pattern was further confirmed by in vitro calpain-1 proteolysis. Futhermore, calpectin and MDL28170, inhibitors of calpain activity, blocked calpain-1-mediated spectrin cleavage. Spectrin cleavage likely occurred in the absence of overt synaptic loss, as suggested by the preserved levels of synaptophysin. Among pharmacological agents tested, apocynin, NADPH oxidase inhibitor, ameliorated the LLP-1-induced spectrin. Given the role of spectrin essential for synapse stabilization, LLP-1-induced spectrin cleavage as occurs with the activation of calpain-1 may be an important effector in LLP-1mediated cell injury in hippocampus, which is primarily linked to cognitive dysfunction.

Kinesin Superfamily KIF5 Proteins Bind to betaIII Spectrin

The kinesin proteins (KIFs) make up a large superfamily of molecular motors that transport cargo such as vesicles, protein complexes, and organelles. KIF5 is a heterotetrameric motor that conveys vesicles and plays an important role in neuronal function. Here, we used the yeast two-hybrid system to identify the neuronal protein (s) that interacts with the tail region of KIF5 and found a specific interaction with betaIII spectrin. The amino acid residues between 1394 and 1774 of betaIII spectrin were required for the interaction with KIF5C. betaIII spectrin also bound to the tail region of neuronal KIF5A and ubiquitous KIF5B but not to other kinesin family members in the yeast two-hybrid assay. In addition, these proteins showed specific interactions, confirmed by GST pull-down assay and co-immunoprecipitation. betaIII spectrin interacted with GST-KIF5 fusion proteins, but not with GST alone. An antibody to betaIII spectrin specifically co-immunoprecipitated KIF5s associated with betaIII spectrin from mouse brain extracts. These results suggest that KIF5 motor proteins transport vesicles or organelles that are coated with betaIII spectrin.

A Case of Congenital Microspherocytosis Requiring Early Splenectomy

Microspherocytosis is known as a hallmark of hereditary spherocytosis (HS) which is one of the most common hemolytic anemias with a prevalence of one per 5000, and is inherited as Mendelian dominant. In this disorder, the patient's red cells become spheroidal, osmotically less resistant in the peripheral circulation, and are selectively trapped in the spleen, but survive normally after splenectomy. The exact mechanism for the formation of microspherocytosis has not been elucidated, although extensive investigations demonstrate that HS red cells are intrinsiclly defective and the patient's spleen does "condition" the metabolically abnormal red cells. The authors report here, one case of severe microspherocytosis in which changes in facial bone structure and transfusion dependency are noted, and an early splenectomy is indicated.