Phenotypic and biochemical analysis of an international cohort of individuals with variants in NAA10 and NAA15.

N-alpha-acetylation is one of the most common co-translational protein modifications in humans and is essential for normal cell function. NAA10 encodes for the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex. The auxiliary and regulatory subunits of the NatA complex are NAA15 and Huntington-interacting protein (HYPK), respectively. Through a genotype-first approach with exome sequencing, we identified and phenotypically characterized 30 individuals from 30 unrelated families with 17 different de novo or inherited, dominantly acting missense variants in NAA10 or NAA15. Clinical features of affected individuals include variable levels of intellectual disability, delayed speech and motor milestones and autism spectrum disorder. Additionally, some subjects present with mild craniofacial dysmorphology, congenital cardiac anomalies and seizures. One of the individuals is an 11-year-old boy with a frameshift variant in exon 7 of NAA10, who presents most notably with microphthalmia, which confirms a prior finding with a single family with Lenz microphthalmia syndrome. Biochemical analyses of variants as part of the human NatA complex, as well as enzymatic analyses with and without the HYPK regulatory subunit, help to explain some of the phenotypic differences seen among the different variants.

Diabetic Ketoacidosis Unmasking a Diagnosis of Glucose-6-Phosphate Dehydrogenase Deficiency: A Case Report and Literature Review.

Glucose-6-phosphate dehydrogenase deficiency (G6PD) is the most common enzyme deficiency. Mode of inheritance is X-linked recessive with a high prevalence in endogamous marriages, such as Jehovah's Witness. Oxidative triggers such as infection, ingestion of certain medications, certain types of food, and in rare instances diabetic ketoacidosis (DKA) may unmask the diagnosis by triggering a hemolytic event. We describe the case of a 43-year-old male with type 2 diabetes who presented with DKA and subsequently became anemic four days after his admission, with the hemoglobin continuing to fall. After extensive workup, it was found that the patient had G6PD confirmed by a low glucose-6-phosphate dehydrogenase assay. We hypothesized that the oxidative stress from the DKA unmasked G6PD induced hemolysis in our patient. During our literature search, we also noticed that hemolysis was delayed on average by four to seven days in these patients after the initiation of insulin therapy similar to our patient. It is postulated that the delayed onset of hemolysis may be due to high levels of glucose in the blood. Hyperglycemia may offset the effects of G6PD deficiency by increasing the production of G6PD. When the levels of glucose start falling, hemolysis becomes apparent.

Economic losses due to infection by apple scar skin viroid in Himachal Pradesh, India.

Apple scar skin viroid (ASSVd), the type member of the genus Apscaviroid, induces symptoms only on fruits, which include colour dappling, russeting, cracking and distortion. Studies on viroid incidence were conducted during past five years and incidence up to 90.0 percent was recorded in commercial apple cultivars (Royal Delicious, Red Delicious, Red Gold, Golden Delicious). From 2015 to 2018, forty apple orchards were surveyed in different blocks of Shimla district of Himachal Pradesh and fruits in six orchards were found with typical symptoms of apple scar skin viroid infection without symptoms on leaves. The presence of ASSVd in symptomatic fruits and symptomless leaves were confirmed by RT- PCR. It was also revealed that ASSVd infection not only deteriorate the quality of apple fruits but cause large losses in term of yield, as 17.80 quintal less fruit production was recorded in the affected orchards with loss in net return up to Rs. 3,91,102/- per hectare (72.68% loss in net return per hectare).

Protein tyrosine phosphatase SHP-1: resurgence as new drug target for human autoimmune disorders.

Recognition of self-antigen and its destruction by the immune system is the hallmark of autoimmune diseases. During the developmental stages, immune cells are introduced to the self-antigen, for which tolerance develops. The inflammatory insults that break the immune tolerance provoke immune system against self-antigen, progressively leading to autoimmune diseases. SH2 domain containing protein tyrosine phosphatase (PTP), SHP-1, was identified as hematopoietic cell-specific PTP that regulates immune function from developing immune tolerance to mediating cell signaling post-immunoreceptor activation. The extensive research on SHP-1-deficient mice elucidated the diversified role of SHP-1 in immune regulation, and inflammatory process and related disorders such as cancer, autoimmunity, and neurodegenerative diseases. The present review focalizes upon the implication of SHP-1 in the pathogenesis of autoimmune disorders, such as allergic asthma, neutrophilic dermatosis, atopic dermatitis, rheumatoid arthritis, and multiple sclerosis, so as to lay the background in pursuance of developing therapeutic strategies targeting SHP-1. Also, new SHP-1 molecular targets have been suggested like SIRP-α, PIPKIγ, and RIP-1 that may prove to be the focal point for the development of therapeutic strategies.