Whole exome sequencing reveals a BSCL2 mutation causing progressive encephalopathy with lipodystrophy [PELD] in an Iranian pediatric patient

Background: Progressive encephalopathy with or without lipodystrophy is a rare autosomal recessive childhoodonset seipin-associated neurodegenerative syndrome, leading to developmental regression of motor and cognitive skills. In this study, we introduce a patient with developmental regression and autism. The causative mutation was found by exome sequencing

Methods: The proband showed a generalized hypertonia and regression of all developmental milestones. Based on the advantages of next-generation sequencing [NGS], whole exome sequencing [WES] was requested. The functional significance of variants was evaluated by NGS-specific prediction servers. Sanger sequencing was used for segregation analysis in the family

Results: There was no specific sign in the clinical and paraclinical investigations of the patient to establish a conclusive clinical diagnosis. WES detected a known homozygous nonsense mutation in BSCL2 [NM_001122955.3:c.985C>T; p.Arg329*]. The variant is segregating in the pedigree with an autosomal recessive pattern

Conclusion: Exome sequencing is a robust method for identifying the candidate gene variants in Mendelian traits

ELISA cut-off point for the diagnosis of human brucellosis; a comparison with serum agglutination test

Brucellosis is a world-wide disease, which has a diverse clinical manifestation, and its diagnosis has to be proven by laboratory data. Serum agglutination test [SAT] is the most-widely used test for diagnosing brucellosis. The enzyme linked immunosorbent assay [ELISA] can also determine specific antibody classes against brucella. It is a sensitive, simple and rapid test, which could be an acceptable alternative to SAT with fewer limitations, however, like any other new test it should be further evaluated and standardized for various populations. This study was planned to determine an optimal cut-off point, for ELISA which would offer maximum sensitivity and specificity for the test when compared to SAT. Four hundred and seven patients with fever and other compatible symptoms of brucellosis were enrolled in the study. Serum agglutination test, 2-Mercaptoethanol test, and ELISA were performed on their sera. The cut-off point of 53 IU/ml of ELISA-IgG yielded the maximal sensitivity and specificity comparing to the other levels of ELISA-IgG, and was considered the best cut offpoint of ELISA-IgG to diagnose acute brucellosis. At this cutoff, the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio were 84.09%, 85.38%, 62.20, 94.90, 5.75, 0.18, respectively. The best cut-off point of ELISA-IgG is 53 IU/ml, which yields the maximal sensitivity and specificity to diagnose acute brucellosis