👤 Abdulrahman Alasmari

Golgi_traff is a Pfam clan containing two members, Dymeclin (DYM) and HID1 domain-containing protein (HID). Interrogation of over 900 eukaryotic genomes with sequence models showed that both are ancient eukaryotic genes, which have exhibited different paths of gene loss, including from major taxonomic groups. For example, the Metazoa have both genes, whereas the Viridiplantae and Dikarya have lost HID and DYM, respectively. A unique replication event occurred within the genus Schizosaccharomyces in that all sequenced species possess three HID-encoding paralogs, whereas its nearest fungal relatives and other eukaryotes are almost exclusively monogenic. A phylogenetic analysis of yeasts revealed that the Golgi-resident paralog Human ortholog 3 (SPAC17A5.16) is more similar to the HID of other yeasts than to its paralogs. Transmission electron microscopy revealed that the SPAC17A5.16 mutant lacks a stacked Golgi apparatus (GA) form, suggesting a role in maintaining GA structure. Altered proliferation of the SPAC17A5.16 mutant in response to GA disrupting chemical agents indicated a perturbation of GA-related functions. Structural models suggest SPAC17A5.16 has a long, disordered N-terminal region that may facilitate anchoring to GA membranes. A modification to Schizosaccharomyces HID nomenclature is proposed to reflect their evolutionary and functional characteristics. The potential of the Golgi_traff clan to serve as a model for the diversification of protein function according to the concepts of sub/neofunctionalization is discussed. Show less

Dyggve-Melchior-Clausen (DMC) syndrome is an autosomal skeletal dysplasia, caused by mutations in the DYM gene. The features of this condition include developmental delay skeletal deformity, coarse facial features, and skeletal abnormalities. This case report presents a novel mutation association between DMC syndrome and celiac disease, emphasizing unique clinical findings and management strategies. This case report presents the case of an eight-year-old boy from Saudi Arabia, born to consanguineous parents. The patient presented with delayed development, coarse facial features, skeletal deformity, and fused toes. Radiological findings showed hallmark features of DMC syndrome such as a double hump appearance of the spine, short tubular metacarpal bones, and a lacy pattern on the iliac crest. A homozygous pathogenic mutation in the DYM gene was confirmed by whole-exome sequencing. Furthermore, the patient had celiac disease serology positive. To our knowledge, we did not find any case of DMC syndrome and celiac disease. This case expands the clinical spectrum of DMC syndrome by documenting its association with celiac disease, a previously unreported comorbidity. It underscores the importance of comprehensive evaluation, including autoimmune screening, in patients with rare genetic disorders. Further research is needed to explore the potential link between DMC syndrome and autoimmune conditions. Show less

Brain channelopathies represent a growing class of brain disorders that usually result in paroxysmal disorders, although their role in other neurological phenotypes, including the recently described NALCN-related infantile encephalopathy, is increasingly recognized. In three Saudi Arabian families and one Egyptian family all affected by a remarkably similar phenotype (infantile encephalopathy and largely normal brain MRI) to that of NALCN-related infantile encephalopathy, we identified a locus on 2q34 in which whole-exome sequencing revealed three, including two apparently loss-of-function, recessive mutations in UNC80. UNC80 encodes a large protein that is necessary for the stability and function of NALCN and for bridging NALCN to UNC79 to form a functional complex. Our results expand the clinical relevance of the UNC79-UNC80-NALCN channel complex. Show less