Clinical and genetic analysis of a patient with Desminopathy manifesting initially with myalgia after lower limb activity / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic variant of a patient with desminopathy manifesting with atypical symptoms.@*METHODS@#A patient who was admitted to the Department of Neurology of Jing'an District Central Hospital on February 24, 2021 was selected as the study subject. Clinical data, laboratory tests, muscle pathology, muscle magnetic resonance imaging (MRI) and genetic testing of the patient were retrospectively analyzed.@*RESULTS@#The patient had developed myalgia after lower limb activity, and gradually developed asymmetrical muscle weakness and atrophy of the lower limbs. Cardiac examination revealed atrioventricular block and decreased left ventricular diastolic function. Muscle MRI showed that semitendinosus, sartorius, gracilis, fibula, gastronemius and supinator muscles were selectively involved at the early stage. Muscle biopsy confirmed pathological changes of desmin positive myofibrils. Genetic testing revealed that the patient has harbored a c.1024A>G (p.n342d) missense variant in exon 6 of the DES gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PS4_moderate+PM2_supporting+PP3_moderate+PP1).@*CONCLUSION@#Desmin disease has a great clinical heterogeneity. Postexercise myalgia of lower limbs is a rare clinical phenotype. For patients harboring the c.1024A>G (p.n342d) variant of the DES gene, in addition to semitendinosus and fibula, Cardiac involvement is relatively insidious and easy to be ignored in clinic. Timely muscle MRI, muscle biopsy and gene detection will help the early diagnosis of the disease.

Clinical and imaging characteristics of patients with unruptured intracranial aneurysms accompanied by sentinel headache / 中华神经医学杂志

Objective:To explore the clinical and imaging characteristics of patients with unruptured intracranial aneurysms accompanied by sentinel headache.Methods:Forty patients with unruptured intracranial aneurysms confirmed by DSA/CTA and accompanied by sentinel headache admitted to Department of Neurology, First Affiliated Hospital of Xiangnan University from January 2018 to August 2023 were selected as the study subjects; the clinical and imaging characteristics of these patients were summarized. Forty-four patients with unruptured intracranial aneurysms without sentinel headache and 40 patients with subarachnoid hemorrhage caused by ruptured intracranial aneurysms admitted to the hospital at the same period were selected as controls. The differences in aneurysm length (maximum diameter), morphology, tumor length (maximum diameter)/neck width (AR), and risk score for rupture of intracranial aneurysms (scores of population, hypertension, age, size of aneurysm, earlier aneurysm rupture, site of aneurysm [PHASES]) among the 3 groups were analyzed.Results:Among the 40 patients with unruptured intracranial aneurysms accompanied by sentinel headache, 20 (50%) presented with pain localized at the lateral frontal and orbital regions, 3 (7.5%) with pain at the posterior neck region, and 17 (42.5%) with irregular headache sites; 34 (85%) had new onset headache, and 6 (15%) had changes in headache nature besides chronic headache; 24 patients (60%) had posterior communicating artery aneurysm, 12 (30%) had internal carotid artery aneurysm, 1 (2.5%) had middle cerebral artery aneurysm, and 3 (7.5%) had vertebral artery dissection aneurysm; 36 (90%) had irregular aneurysm morphology. Compared with patients with unruptured intracranial aneurysms without sentinel headache, patients with unruptured intracranial aneurysms accompanied by sentinel headache and those with subarachnoid hemorrhage caused by ruptured intracranial aneurysms had larger aneurysm length (maximum diameter), higher proportion of irregular morphology, higher AR value, and higher PHASES scores, with significant differences ( P<0.05). Compared with patients with subarachnoid hemorrhage caused by ruptured intracranial aneurysms, patients with unruptured intracranial aneurysms accompanied by sentinel headache had larger aneurysm length (maximum diameter) and higher PHASES scores, with significant differences ( P<0.05). Conclusion:Sentinel headache is common in patients with unruptured posterior communicating artery aneurysms, and the relatively specific headache pattern is sudden periorbital pain or posterior neck pain; patients with unruptured intracranial aneurysms accompanied by sentinel headache have a higher rupture risk due to the larger size, more irregular shape, higher AR value of the aneurysm, therefore, same attention should be payed to these patients as those with ruptured aneurysms in clinical practice.

Clinical and neuroimaging features of spontaneous convexal subarachnoid hemorrhage complicated with acute cerebral infarction / 中华神经医学杂志

Objective:To investigate the clinical and imaging features of spontaneous convexal subarachnoid hemorrhage (cSAH) with acute cerebral infarction.Methods:Nine patients with cSAH complicated with acute cerebral infarction, admitted to our hospital from January 2018 to October 2021, were selected. The clinical data and efficacy of these patients were retrospectively analyzed.Results:The time from cSAH to the onset of acute cerebral infarction was 5-144 h, with median time of 2 d. The most common bleeding site of cSAH was the parietal lobe ( n=6); cSAH in the ipsilateral side of acute cerebral infarction was noted in 4 patients. Six patients had middle cerebral artery stenosis or occlusion, and 2 patients had anterior cerebral artery stenosis or occlusion. Hypertension ( n=7) was the most common primary disease; 7 patients were treated with antiplatelet drugs, anticoagulants and/or stents. The follow-up at 3 months after cSAH showed that 6 patients had good prognosis and one had poor prognosis. Conclusions:The cSAH often occurs 2 d after acute cerebral infarction; intracranial artery stenosis or occlusion may be the main cause of the disease. In patients complicated with cSAH, active antiplatelet, anticoagulation and/or stent therapy do not increase the risk of bleeding, and the prognosis is good.

Role of sphingolipids signaling in pathogenesis of pulmonary fibrosis / 中国药理学与毒理学杂志

Pulmonary fibrosis is a group of chronic lung diseases caused by various factors and characterized by chronic inflammations,lung tissue structure damage,increase of pulmonary interstitial collagen and massive deposition of extracellular matrix (ECM). Because of its complicated etiology, there is no effective treatment currently. Recent studies showed that the activation of sphingolipids signaling and pulmonary fibrosis were closely related. This paper describes the composition and function of sphingolipids signaling pathway and its effect on fibrosis in order to provide new ideas about further study of the pathogenesis of pulmonary fibrosis and methods of prevention.

Studies on the CAG repeat expansion in patients with hereditary spinocerebellar ataxia from Chinese Han / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the CAG trinucleotide repeat expansion in spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7, 12, and 17 from Chinese Han.</p><p><b>METHODS</b>The pathological CAG triplet repeat expansions of the SCA1, SCA2, SCA3/Machado-Joseph disease (MJD), SCA6, SCA7, SCA12 and SCA17 genes were analyzed in a cohort of 559 Mainland Chinese patients affected by spinocerebellar ataxia, including 363 probands from families with autosomal dominant SCA and 196 sporadic cases. Polymerase chain reaction, agarose gel electrophoresis, recombinant DNA technology by T-vector cloning and direct sequencing were performed to detect the CAG-repeat number of abnormal allele.</p><p><b>RESULTS</b>Among the 559 SCA patients, twenty-three were positive for SCA1, the ranges of expanded CAG repeats were from 39 to 60 (mean:51.09+/-4.88); thirty-two were positive for SCA2, the ranges of expanded CAG repeats were from 36 to 51 (mean:40.34+/-4.40); three hundred and five were positive for SCA3/MJD, the ranges of expanded CAG repeats were from 49 to 86 (mean:73.84+/-5.07); nine were positive for SCA6, the ranges of expanded CAG repeats were from 23 to 29 (mean:25.56+/-1.94); twenty-seven were positive for SCA7, the ranges of expanded CAG repeats were from 38 to 71(mean:58.22+/-10.90); three were positive for SCA12, the ranges of expanded CAG repeats were from 51 to 52 (mean:51.33+/-0.58); and finally, two were positive for SCA17, the range of expanded CAG repeats were from 53 to 55 (mean:54.00+/-1.41).</p><p><b>CONCLUSION</b>The 39 CAG repeats of SCA1, 49 CAG repeats of SCA3 and 51 CAG repeats of SCA12 are all the shortest known causative expanded alleles, while the 86 CAG repeats of SCA3/MJD is the largest full expanded allele that has never been reported. Furthermore, it is the first report of SCA17 subtype in Mainland Chinese and first research that established the abnormal reference standard of CAG repeat number of different subtypes of SCA in Chinese Han.</p>

Frequency of spinocerebellar ataxia types 1, 2, 3, 6, 7, 8, 10, 12, 17 and dentatorubral-pallidoluysian atrophy in Chinese Han population / 中华神经科杂志

Objective To assess the frequency of different subtype of spinocerebellar ataxias (SCAs) in Chinese Han population. Methods The nueleotide repeat mutations of SCA1, SCA2, SCA3/ MJD, SCA6, SCAT, SCA8, SCA10, SCA12, SCA17 and dentatorubral-pallidoluysian atrophy (DRPLA) were detected by the polymerase chain reaction (PCR), denaturing polyacrylamide gel electrophoresis (PAGE), Southern blot, recombinant DNA technology by T-vector cloning and direct sequencing technique in a cohort of 559 Mainland Chinese patients affected by spinocerebellar ataxia, including 363 families with autosomal dominant SCA (AD-SCA) and 196 sporadic cases. Results Among the 363 AD-SCA families, 15 families (4. 13%) were positive for SCA1, 26 (7. 16%) for SCA2, 187 (51.52%) for SCA3/MJD, 6 (1.65%) for SCA6, 7 (1.93%) for SCA7, 1 (0. 28%) for SCA12 and 1 (0. 28%) positive for SCA17; 120(33. 06%) were negative for all the tested SCAs. There were 2 (1.02%) SCAI, 3 (1.53%) SCA2, 15 (7. 65%) SCA3/MJD, 3 (1.53%) SCA6 and 173 (88.27%) not identified in the 196 sporadic SCA patients. None of the SCA8, SCA10 and DRPLA mutation was found. Conclusions SCA3/MJD is a substantially common subtype of AD-SCAs and sporadic SCA in Chinese Han patients with SCAs, subsequently followed by SCA2, SCA1, SCAT and SCA6; SCA12 and SCA17 are uncommon subtypes, while SCA8, SCA10, and DRPLA are rare, if not absent. SCA17 subtype was initially identified in mailand China. Some other genes might be causative in those unidentified AD-SCA pedigrees, and other etiological factors besides genetic cause might contribute for those sporadic cases.

Study on the single-nucleotide substitution (c.-16C to T) of the PURATROPHIN-1 gene in Chinese patients with spinocerebellar ataxia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the single-nucleotide substitution (c.-16C to T) of the PURATROPHIN-1 gene in spinocerebellar ataxia (SCA) patients in China.</p><p><b>METHODS</b>The single-nucleotide substitution (c.-16C to T) of the PURATROPHIN-1 gene was detected by PCR, digested with EcoN I, separated on 8% polyacrylamide gel in 68 probands of autosomal dominant SCA families and 119 sporadic SCA patients, who had been excluded CAG/CAA repeat expansion at the SCA1, 2, 3, 6, 7, 17 and dentatorubral-pallidolluysian atrophy (DRPLA) loci. The results were confirmed in four patients by direct sequencing.</p><p><b>RESULTS</b>The single-nucleotide substitution (c.-16C to T) of the PURATROPHIN-1 gene was not identified in authors' cohort.</p><p><b>CONCLUSION</b>The mutation of c.-16C to T of the PURATROPHIN-1 gene might be rare in SCA patients in China.</p>