Whole exome sequencing identifies a novel compound heterozygous GFM1 variant underlying developmental delay, dystonia, polymicrogyria, and severe intellectual disability in a Pakhtun family.

Mitochondrial protein synthesis requires three elongation factors including EF-Tu (TUFM; OMIM 602389), EF-Ts (TSFM; OMIM 604723), and EF-G1 (GFM1; OMIM 606639). Pathogenic variants in any of these three members result in defective mitochondrial translation which can impart an oxidative phosphorylation (OXPHOS) deficiency. In this study, we investigated a consanguineous Pakhtun Pakistani family. There were four affected siblings at the time of this study and one affected girl had died in infancy. The index patient had severe intellectual disability, global developmental delay, dystonia, no speech development, feeding difficulties, and nystagmus. MRI brain presented thinning of corpus callosum and polymicrogyria. Whole exome sequencing revealed a novel compound heterozygous variant in GFM1 located on chromosome 3q25.32. Sanger sequencing confirmed recessive segregation of the maternal (NM_001308164.1:c.409G > A; p.Val137Met) and paternal (NM_001308164.1:c.1880G > A; p.Arg627Gln) variants in all the four affected siblings. These variants are classified as "likely-pathogenic" according to the recommendation of ACMG/AMP guideline. GFM1 alterations mostly lead to severe phenotypes and the patients may die in early neonatal life; however, four of the affected siblings had survived till the ages of 10-17 years, without developing any life-threatening conditions. Mostly, in cousin marriages, the pathogenic variants are identical-by-descent, and affected siblings born to such parents are homozygous. Three homozygous variants were shortlisted in the analysis of the WES data, but Sanger sequencing did not confirm their segregation with the disease phenotype. This is the first report from Pakistan expanding pathogenicity of GFM1 gene.

Knowledge assessment of radiologists, radiology residents, and radiographers regarding contrast materials and management of adverse drug reactions occurring due to contrast materials: a cross-sectional study.

The purpose of this study was to assess the knowledge of the radiology personnel regarding contrast media used in radiology and the management of associated adverse drug reactions. Methods: A questionnaire-based cross-sectional study was conducted from 21 February to 31 March 2019 in five major hospitals of Peshawar, Pakistan. A 30-item questionnaire was adopted from the existing literature containing both open and closed-ended questions and the authors conducted a pilot study among 25 participants to assess the face validity of the tool. A universal sampling technique was adopted. Descriptive statistics were used to summarize the findings of the study. Results: Less than half of the participants could correctly classify iodinated contrast media used in radiology on the basis of ionicity and osmolaity. Sixty-three percent chose severe contrast material-induced allergic reaction as type I hypersensitivity reaction while almost half of them correctly identified the features of iodinated contrast media associated with lesser side effects. Very few of them (6.7%) had read the ACR 2018 manual on contrast media. Regarding the risk factors for acute adverse reactions and signs/symptoms of anaphylaxis few could answer satisfactorily. Twenty-eight percent of participants correctly identified epinephrine as the initial medication in an anaphylactic reaction. Regarding the preferred route of administration, concentration and dose of epinephrine, the participants' correct response was quite poor (43.8%, 6.7%, and 8.6%, respectively). More than 65% of participants could name a single intravenous corticosteroid and antihistamine. Conclusion: Radiology personnel's knowledge regarding contrast material and management of severe contrast material-induced allergic reactions is unsatisfactory.