ABSTRACT
OBJECTIVE@#To explore the clinical and genetic characteristics of a patient with hypertrophic cardiomyopathy as the initial manifestation of Mucopolysaccharidosis type Ⅲ A (MPS Ⅲ A).@*METHODS@#A female patient with MPS Ⅲ A who was admitted to the Affiliated Hospital of Jining Medical University in January 2022 and her family members (seven individuals from three generations) were selected as the study subjects. Clinical data of the proband were collected. Peripheral blood samples of the proband was collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. Heparan-N-sulfatase activity was determined for the disease associated with the variant site.@*RESULTS@#The proband was a 49-year-old woman, for whom cardiac MRI has revealed significant thickening (up to 20 mm) of left ventricular wall and delayed gadolinium enhancement at the apical myocardium. Genetic testing revealed that she has harbored compound heterozygous variants in exon 17 of the SGSH gene, namely c.545G>A (p.Arg182His) and c.703G>A (p.Asp235Asn). Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PM2_Supporting +PM3+PP1Strong+PP3+PP4; PS3+PM1+PM2_Supporting +PM3+PP3+PP4). Sanger sequencing confirmed that her mother was heterozygous for the c.545G>A (p.Arg182His) variant, whilst her father, sisters and her son were heterozygous for the c.703G>A (p.Asp235Asn) variant. Determination of blood leukocyte heparan-N-sulfatase activity suggested that the patient had a low level of 1.6 nmol/(g·h), whilst that of her father, elder and younger sisters and son were all in the normal range.@*CONCLUSION@#The compound heterozygous variants of the SGSH gene probably underlay the MPS ⅢA in this patient, for which hypertrophic cardiomyopathy is an associated phenotype.
Subject(s)
Female , Humans , Male , Middle Aged , Cardiomyopathy, Hypertrophic , Contrast Media , East Asian People , Gadolinium , Mucopolysaccharidosis III , Mutation , PedigreeABSTRACT
Objective To investigate the strategies of reducing the incidence of missed diagnosis of severe traumatic brain injuries combined with multiple trauma. Methods Data of 432 patients with severe traumatic brain injuries and multiple trauma (ISS≥20) from January 2000 to August 2007 were analyzed retrospectively. All patients were divided into missed diagnosis group (MD group, n =54) and non-missed diagnosis group (NMD group, n =378) for correlation analysis on ISS, GCS, anatomical locations of the missed diagnosis, the time of delayed diagnosis and the prognosis. Results ISS was (42.97±10.94) points in MD group, with statistical difference compared with NMD group (P < 0.05). The patients with GCS≤8 in MD group was more than those in NMD group (P < 0.05). Conclusions It is effective to prevent missed diagnosis and improve the survival of patients with severe traumatic brain injuries combined with multiple trauma by judging injury severity quickly and precisely based on the principle of "life first" and repeated and systemic physical examination.