Pathogenic variants in the Golgi localised alpha 1,6 fucosyltransferase, FUT8, cause a rare inherited metabolic disorder known as FUT8‐CDG. To date, only three affected individuals have been reported presenting with a constellation of symptoms including intrauterine growth restriction, severe delays in growth and development, other neurological impairments, significantly shortened limbs, respiratory complications, and shortened lifespan. Here, we report an additional four unrelated affected individuals homozygous for novel pathogenic variants in FUT8. Analysis of serum N‐glycans revealed a complete lack of core fucosylation, an important diagnostic biomarker of FUT8‐CDG. Our data expands both the molecular and clinical phenotypes of FUT8‐CDG and highlights the importance of identifying a reliable biomarker for confirming potentially pathogenic variants.

Background and Objectives: Hereditary hearing loss (HL) is known by a very high genetic heterogeneity, which makes a molecular diagnosis problematic. Next-generation sequencing (NGS) is a new strategy that can overcome this problem. Method: A comprehensive family history was obtained, and clinical evaluations and pedigree analysis were performed in the family with 3 affected members. After excluding mutations in the GJB2 and 7 other most common autosomal recessive nonsyndromic HL genes via Sanger sequencing and genetic linkage analysis in the family, we applied the Otogenetics deafness NGS panel in the proband of this family. Results: NGS results showed a novel rare variant (c.7720C>T) in the MYO15A gene. This nonsense variant in the exon 40 of the MYO15A gene fulfills the criteria of being categorized as pathogenic according to the American College of Medical Genetics and Genomics guideline. Conclusions: New DNA sequencing technologies could lead to identification of the disease causing variants in highly heterogeneous disorders such as HL.

Genetic factors play an important role in the pathogenesis of schizophrenia. Dysregulations in the dopaminergic system have long been known to play an influential role in the development of this disorder. Although a large number of studies have investigated the association between genetic polymorphisms in the genes involved in this system and the risk of schizophrenia, the results have been inconsistent. In this meta-analysis, we searched for publications in Ovid Medline, Embase, Web of Science (science citation index expanded), and PsycNET for articles published until January 2020. We identified case-control studies investigating the association between four common genetic polymorphisms (rs6277, rs1799732, rs1800497, and rs1801028) and the risk of schizophrenia. The studies were subsequently selected according to the predefined inclusion and exclusion criteria. The data extraction was conducted according to the PRISMA guidelines. We also assessed the quality of the studies and investigated publication bias using funnel plot and Egger's regression test. The association analysis was conducted in allelic, dominant, and recessive genetic models. Subsequently, bioinformatics analysis of the effect of the polymorphisms found to be significantly associated with schizophrenia on protein stability, posttranslational modifications, and 3D protein structure was conducted. This meta-analysis showed that Taq1A (allelic model: OR, 0.856, 95% CI, 0.734-0.998) has a protective effect against the development of schizophrenia. Further, it was found that this variant may decrease ANKK1 protein stability. Further, this polymorphism was found to lead to the gain of modifications sites for ubiquitination (Ubi. score = -1.894) and methylation (Meth. score = -0.834). Several genetic factors contribute to the susceptibility of schizophrenia. The updated knowledge emerging from this meta-analysis showing the protective effect of rs1800497 polymorphism (Taq1A) can shed light on the role of Taq1A polymorphism in the susceptibility to schizophrenia and also pave way for further functional studies investigating the role of ANKK1 protein in the pathogenesis of schizophrenia.

NGS is very promising to identify the molecular etiology of highly heterogeneous diseases such as HL. MARVELD2 might be important in the etiology of HL in this region of Iran.

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