Novel Optineurin Frameshift Insertion in a Family With Frontotemporal Dementia and Parkinsonism Without Amyotrophic Lateral Sclerosis.

Frontotemporal Dementia (FTD) is a common cause of Young Onset Dementia and has diverse clinical manifestations involving behavior, executive function, language and motor function, including parkinsonism. Up to 50% of FTD patients report a positive family history, supporting a strong genetic basis, particularly in cases with both FTD and amyotrophic lateral sclerosis (FTD-ALS). Mutations in three genes are associated with the majority of familial FTD (fFTD) cases - microtubule associated protein tau gene (MAPT), granulin precursor (GRN), and hexanucleotide repeat expansions in chromosome 9 open reading frame 72- SMCR8complex subunit (C9orf72) while mutations in other genes such as optineurin (OPTN) have rarely been reported. Mutations in OPTN have been reported mostly in familial and sporadic cases of ALS, or in rare cases of FTD-ALS, but not in association with pure or predominant FTD and/or parkinsonian phenotype. Here, we report for the first time, a family from the Philippines with four members harboring a novel frameshift insertion at OPTN (Chr 10:13166090 G>GA) p.Lys328GluTer11, three of whom presented with FTD-related phenotypes. Additionally, one sibling heterozygous for the frameshift insertion had a predominantly parkinsonian phenotype resembling corticobasal syndrome, but it remains to be determined if this phenotype is related to the frameshift insertion. Notably, none of the affected members showed any evidence of motor neuron disease or ALS at the time of writing, both clinically and on electrophysiological testing, expanding the phenotypic spectrum of OPTN mutations. Close follow-up of mutation carriers for the development of new clinical features and wider investigation of additional family members with further genetic analyses will be conducted to investigate the possibility of other genetic modifiers in this family which could explain phenotypic heterogeneity.

Association of lipoprotein lipase gene polymorphisms with coronary artery disease among Filipinos.

Studies have shown association of lipoprotein lipase (LPL) polymorphisms with coronary artery disease (CAD); however, limited studies on the genetics of CAD have been done in the Philippines. Because of their effects on high-density lipoprotein and triglyceride metabolism, the G-allele of the Ser447X variant of LPL gene has been shown to be atheroprotective, while HindIII polymorphism has been shown to be pro-atherogenic. We assessed 1301 patients undergoing coronary angiography to determine the prevalence of HindIII and Ser447X polymorphisms and their association with angiographically significant CAD. Genotyping for HindIII and Ser447X variants were analyzed by real-time PCR. Multivariate analyses were performed to determine the interaction between LPL polymorphisms and risk factors of CAD. CAD+ group (72%) was predominantly male (76%) with a mean age of 60.17 ± 11.01 with hypertension (89%), dyslipidemia (84%) and smoking (54%) as the most common risk factors. HindIII carriage frequency among the CAD+ group was 20.3% with a genotypic distribution of 78.71% (T/T), 19.83% (T/G) and 1.46% (G/G). Ser447X carriage frequency among the CAD+ group was 8.0% with a genotypic distribution of 91.39% (C/C), 8.38% (C/G) and 0.23% (G/G). HindIII and Ser447X polymorphisms were both not significantly associated with CAD. LPL polymorphic allele HindIII was common, while Ser447X was rare. Present study did not show association of LPL polymorphisms with the development of CAD. However, among patients with dyslipidemia, presence of Ser447X allele is associated with an increased risk (OR 2.6; 95% CI 2.1-3.7; p value < 0.001) of developing CAD than those without LPL polymorphisms.

Molecular diagnosis of acute retinal necrosis secondary to cytomegalovirus in vitreous aspirate.

We report a case of a 45-year old Filipino post-kidney transplant patient maintained on steroids, who presented with floaters in her left eye. Vitreous aspirate was analyzed using polymerase chain reaction (PCR) for human cytomegalovirus (HCMV) and herpes simplex virus (HSV). A distinct band (435 bp) was found that confirmed the presence of HCMV. Since a rapid and accurate diagnosis is crucial for prompt administration of antiviral therapy, PCR-based analysis of vitreous aspirate provides a valuable tool in the diagnosis of patients with retinitis caused by herpes viruses.