Hypertrophic cardiomyopathy secondary to deficiency in lysosomeassociated membrane protein-2: A case report

BACKGROUND Danon disease(DD),in which mutations in the X-linked lysosome-associated membrane protein-2(LAMP-2)gene result in hypertrophic cardiomyopathy,is a rare disease,reported primarily in small samples or cases.However,with the development of cardiac magnetic resonance imaging and genetic technology in recent years,the number of reports has increased.CASE SUMMARY We report a case of DD in an adolescent male patient,confirmed by genetic testing.The patient was admitted to our hospital with complaints of a three-year history of chest tightness and shortness of breath.His preliminary clinical diagnosis is hypertrophic cardiomyopathy.Our report includes the patient’s clinical course from hospital admission to death,step-by-step diagnosis,treatment course,and noninvasive imaging features.We highlight how a noninvasive diagnostic approach,based solely on clinical and imaging“red flags”for DD,can be used to achieve a diagnosis of DD with a high degree of confidence.CONCLUSION DD is a very dangerous cardiomyopathy,and it is necessary to achieve early diagnosis and treatment.

Identification of residues in Lassa virus glycoprotein 1 involved in receptor switch

Lassa virus(LASV)is an enveloped,negative-sense RNA virus that causes Lassa hemorrhagic fever.Successful entry of LASV requires the viral glycoprotein 1(GP1)to undergo a receptor switch from its primary receptor alpha-dystroglycan(α-DG)to its endosomal receptor lysosome-associated membrane protein 1(LAMP1).A conserved histidine triad in LASV GP1 has been reported to be responsible for receptor switch.To test the hypothesis that other non-conserved residues also contribute to receptor switch,we constructed a series of mutant LASV GP1 proteins and tested them for binding to LAMP1.Four residues,L84,K88,L107,and H170,were identified as critical for receptor switch.Substituting any of the four residues with the corresponding lymphocytic choriomeningitis virus(LCMV)residue(L84 N,K88E,L10F,and H170S)reduced the binding affinity of LASV GP1 for LAMP1.Moreover,all mutations caused decreases in glycoprotein precursor(GPC)-mediated membrane fusion at both pH 4.5 and 5.2.The infectivity of pseudotyped viruses bearing either GPCL84N or GPCK88E decreased sharply in multiple cell types,while L107F and H170S had only mild effects on infectivity.Using biolayer light interferometry assay,we found that all four mutants had decreased binding affinity to LAMP1,in the order of binding affinity being L84 N>L107F>K88E>H170S.The four amino acid loci identified for the first time in this study have important reference significance for the in-depth investigation of the mechanism of receptor switching and immune escape of LASV occurrence and the development of reserve anti-LASV infection drugs.