Recent studies on dilated cardiomyopathy caused by TTN mutations in children / 中国当代儿科杂志

The mutations of TTN gene that encodes titin are the most common mutation type among the genetic causes of dilated cardiomyopathy (DCM). This article reviews the worldwide studies on potential molecular pathogenesis (transcription, post-translational modification, etc.), clinical phenotypes, and gene therapies of pediatric DCM caused by TTN mutations, with the hope of providing a reference for the precision treatment of pediatric DCM caused by TTN mutations.

Analysis of DSG2, TTN and GATA4 gene variants in patients with Brugada syndrome from Henan / 中华医学遗传学杂志

OBJECTIVE@#To explore the correlation between DSG2, TTN and GATA4 genes and Brugada syndrome in Henan Province of China.@*METHODS@#From February 2017 to February 2019, 100 patients with Brugada syndrome and 100 healthy individuals were selected as the study and the control groups, respectively. Electrocardiogram and echocardiography were carried out, and peripheral blood samples was collected. Coding regions of DSG2, TTN and GATA4 genes were amplified by PCR and sequenced. The results were compared with standard sequences from GenBank.@*RESULTS@#Electrocardiogram showed that all patients from the study group had ventricular arrhythmia, 87 cases (87%) presented ventricular tachycardia (VT), 84 cases (84%) presented T wave inversion, and 51 cases (51%) presented Epsilon wave. Echocardiography showed that the right ventricle in the study group was enlarged with the inner diameter of the right ventricle being (40.0±13.3) mm, and the right ventricle showed various degree of abnormal systolic function. The enlargement of right atrium accounted for 64%, and the involvement of the left ventricle accounted for 27%. The right ventricular diameter and left ventricular diastolic diameter of the study group were significantly greater than those of the control group (P< 0.05). DNA sequencing showed that 60 patients carried DSG2 gene variants, among which 18 had missense variant of exon 8. Fifty patients carried TTN gene variants, including 8 in the A-band domain and 3 in the I-band domain. Twenty patients carried 3 variants of the GATA4 gene.@*CONCLUSION@#Variants of the DSG2, TTN and GATA4 genes in Henan region are correlated with the onset of Brugada syndrome.

Limb-girdle muscular dystrophy type 2G: clinical, pathological and genetic analysis of a case / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate TCAP gene mutation and clinical features of a Chinese patient with limb-girdle muscular dystrophy type 2G(LGMD 2G).</p><p><b>METHODS</b>Clinical data of the patient was analyzed. Exons of the TCAP gene were amplified and sequenced.</p><p><b>RESULTS</b>The patient has presented clinically as LGMD and pathologically as vacuolar myopathy. Genetic analysis has identified compound heterozygous mutations of exons 1 and 2 of the TCAP gene(c.100delC, c.166insG).</p><p><b>CONCLUSION</b>LGMD is a group of neuromuscular disorders with substantial phenotypic heterogeneity. Genetic diagnosis has become indispensable for accurate diagnosis for patients suspected to have the disease.</p>

Changes of sarcoplasmic reticulum calcium ATPase, titin, and nebulin expressions in the diaphragm of rats with liver cirrhosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the molecular mechanisms of diaphragm injury in rats with liver cirrhosis.</p><p><b>METHODS</b>Thirty adult male Sprague-Dawley rats were randomized into control group (n=10) and carbon tetrachloride-induced liver cirrhosis group (LC group, n=20). In the 9th week, the rat body weight and diaphragm to body weight ratio were measured, and the parameters of diaphragm contractility including peak twitch tension (Pt), maximum tetanic tension (Po), time to peak contraction (CT), half relaxation time (1/2RT), and force-frequency curve were assessed using a Medlab-U/4C biological signal collecting system. The activities of superoxide dismutase (SOD), succinic dehydrogenase (SDH) and myeloperoxidase (MPO) and malondiadehyde (MDA) content in the diaphragm were detected. The mRNA expression levels of sarcoplasmic reticulum calcium ATPase (SERCA) and cytoskeletal proteins (titin and nebulin) in the diaphragm were detected by RT-PCR, and the diaphragm ultrastructure was examined with electron microscopy.</p><p><b>RESULTS</b>Compared with those in the control group, body weight, diaphragm to body weight ratio, Pt, Po, and tetanic force under the stimulus frequency of 10, 20, 40, 60, 100 Hz were all significantly decreased (P<0.01), while CT and 1/2RT were significantly prolonged in LC group (P<0.01). SOD and SDH activities were significantly lowered (P<0.01) while the contents of MDA and MPO activity were significantly increased in LC group (P<0.01) with significantly decreased SERCA, titin and nebulin mRNA expressions in the diaphragm (P<0.01). Electron microscopy of the diaphragm in LC group revealed myofibrillar degeneration, absence of the Z line, and mitochondria swelling and edema.</p><p><b>CONCLUSION</b>Liver cirrhosis increases free radicals and aggravates inflammatory response and lipid peroxidation in the diaphragm, thus leading to mitochondrial damages and decreased expressions of cytoskeletal proteins and SERCA to cause diaphragmatic dysfunction.</p>

Titin gene mutations in Chinese patients with dilated cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>Titin is recently known as the largest protein which exists in the striated muscle sarcomere and is dynamic both in biomechanics properties and biochemical functions. Four possible disease-associated mutations located in three exons (3, 14, 49) of titin gene (TTN) have been identified in Japanese DCM patients in 2002. We observed the possible association of TTN mutation in Chinese patients with DCM.</p><p><b>METHODS</b>Three exons of TTN (3, 14, 49) were screened in 117 DCM patients and 120 controls by polymerase chain reaction-single strand conformation polymorphisms (PCR-SSCP) and DNA sequence. SSCP was carried out following a protocol optimized for each PCR fragment after amplification. Abnormal SSCP results were subsequently confirmed by DNA sequencing.</p><p><b>RESULTS</b>The mutations reported in Japanese DCM patients were not identified in this patient cohort. A novel mutation [the G13053A (TTN cDNA sequence, X90568) change resulted in amino acid change at position 4351 (Gly4351Asp)] was found in two young DCM patients from a DCM family (1.7%). There was no similar mutation in controls.</p><p><b>CONCLUSION</b>This novel Gly4351Asp mutation in TTN might be associated with DCM.</p>

Serum anti-titin antibody in patients with myasthenia gravis / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the clinical significance of serum anti-titin antibody level in the diagnosis of myasthenia gravis (MG) with thymoma.</p><p><b>METHOD</b>The serum anti-titin antibody was analysed by ELISA method in 40 cases of health control group, 90 cases of MG, 17 cases of MG with thymoma and 7 cases of no-MG thymoma. The positive rate was compared among these groups.</p><p><b>RESULTS</b>The positive rate of anti-titin antibody was significantly higher in MG with thymoma patients than MG patients (94% and 3%, P < 0.01). According to the Osserman's classification, anti-titin antibody was present mostly in patients (43%) in IV stage, and also present in 2 cases of 7 who with no-MG thymoma.</p><p><b>CONCLUSION</b>Serum anti-titin antibody test is helpful in the diagnosis of MG with thymoma.</p>

Computed tomographic findings in pelvic cavity after radiation therapy for carcinoma of cervix

From July 1, 1981 to August 31, 1984, 59 patients who had radiation therapy for carcinoma of cervix had CTscanning at Departement of Diagnostic Radiology, Kosin Medical College. The authors analysed the CT findings ofthe patients in regard to the recurrence of the disease and postradiation changes. The results are as followings:1. The incidence of recurrence was most common in advanced stage over IIb. 77% 2. Changes in pelvic cavity were asfollowings; ; Widening of presacral space 78% ; Increased perirectal fat space 81% ; Symmetrical thickening ofperirectal fascia 97% ; Fibrous connectin between sacrum and rectum 92% ; Anterior conncetion between rectum andperirectal fascia 47% ; Increased bowel wall thickness 44% ; Increased bladder wall thickness with trabeculations51% 3. In most patients who had CT scanning within 3 months after radiation therapy, CT did not demonstratepostradiation changes characterized by an increased pelvic fibrous and fatty tissue. 4. In 10 patients who hadpostoperative radiation therapy, 8 patients show increased bowel wall thickness. 5. 30 patients with recurrentcarcinoma of cervix were as followings; ; Pelvic tumor recurrence 90% ; Parametrial and side wall extension 53% ;Pelvic and paraaortic lymphadenopathy 40% ; Hydronephrosis 23% ; Bladder involvement 23% ; Lumbar spineinvolvement 10% And 1 patient shows distant metastasis to paraaortic lymph node, 1 patient to lumbar spine, and 1patient to liver without recurrent tumor mass in pelvic cavity. 6. 2 patients showing mass wihout other sign inthe pelvic cavity were unable to be differentiated between irradiated uterus and recurrent tumor.