Mutation Frequency of the Major Frontotemporal Dementia Genes, MAPT, GRN and C9ORF72 in a Turkish Cohort of Dementia Patients

‘Microtubule-associated protein tau’ (MAPT), ‘granulin’ (GRN) and ‘chromosome 9 open reading frame72’ (C9ORF72) gene mutations are the major known genetic causes of frontotemporal dementia (FTD). Recent studies suggest that mutations in these genes may also be associated with other forms of dementia. Therefore we investigated whether MAPT, GRN and C9ORF72 gene mutations are major contributors to dementia in a random, unselected Turkish cohort of dementia patients. A combination of whole-exome sequencing, Sanger sequencing and fragment analysis/Southern blot was performed in order to identify pathogenic mutations and novel variants in these genes as well as other FTD-related genes such as the ‘charged multivesicular body protein 2B’ (CHMP2B), the ‘FUS RNA binding protein’ (FUS), the ‘TAR DNA binding protein’ (TARDBP), the ‘sequestosome1’ (SQSTM1), and the ‘valosin containing protein’ (VCP). We determined one pathogenic MAPT mutation (c.1906C>T, p.P636L) and one novel missense variant (c.38A>G, p.D13G). In GRN we identified a probably pathogenic TGAG deletion in the splice donor site of exon 6. Three patients were found to carry the GGGGCC expansions in the non-coding region of the C9ORF72 gene. In summary, a complete screening for mutations in MAPT, GRN and C9ORF72 genes revealed a frequency of 5.4% of pathogenic mutations in a random cohort of 93 Turkish index patients with dementia

Peripheral GRN mRNA and Serum Progranulin Levels as a Potential Indicator for Both the Presence of Splice Site Mutations and Individuals at Risk for Frontotemporal Dementia

Progranulin (GRN) gene mutations are a major cause of frontotemporal dementia (FTD). Most mutations identified to date are null mutations, which are predicted to cause the pathology via haploinsufficiency. Decreased peripheral progranulin protein (PGRN) levels are associated with the presence of GRN null mutations and are accepted as reliable biomarkers. In this study, our aim was to test whether the presence of specific GRN splice site mutations (c.– 8+2T>G and c.708+6_9del), could be predicted by peripheral mRNA or protein GRN levels, by studying affected and asymptomatic individuals from FTD families. We also tested four missense GRN variants to assess if altered GRN levels depended on the type of mutation. Our results confirmed a reduction in both mRNA and protein PGRN levels in the splice site mutation carriers, which is consistent with previous reports for null mutations. Our results also suggested that both decreased peripheral GRN mRNA and serum PGRN levels indicate the presence of pathogenic mutations in affected individuals, and identify the asymptomatic individuals at risk, without previous knowledge of genetic status. Both inferences suggest a potential use of peripheral GRN mRNA or serum PGRN levels as biomarkers for families with FTD

Mutations in TYROBP are not a common cause of dementia in a Turkish cohort

Mutations in TYROBP and TREM2 have been shown to cause polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy. Recently, variants in TREM2 were also associated with frontotemporal dementia and Alzheimer's disease. Given the functional proximity between these 2 genes, we investigated the genetic variation of TYROBP in a Turkish cohort of 103 dementia patients. No mutations or copy number variants predicted to be pathogenic were identified. These results indicate that mutations in TYROBP are not a common cause of dementia in this Turkish cohort

PROGNOSTIC FACTORS IN MENINGOCOCCAL DISEASE AND A NEW SCORING SYSTEM

One-hundred-and-forty patients diagnosed as having meningococcal disease have been investigated retrospectively with respect to prognostic factors. The overall mortality was 8.6%, the mortality rate of the infants under 6 months of age being higher than that of the other groups. In cases where there was no meningitis or leucocytosis, the presence of hypotension, disturbed consciousness and diffuse petechiae increased the mortality rate significantly. High fever did not have any effect on mortality. We propose a new practical and reliable scoring system for meningococcal disease for determining the influence of prognostic factors on mortality

An outstanding non-transplant surgical intervention in progressive familial intrahepatic cholestasis: partial internal biliary diversion

Progressive familial intrahepatic cholestasis (PFIC) is a hereditary disease with severe cholestasis progressing to cirrhosis and chronic renal failure usually during the first decade. An alternative approach is partial diversion of bile. The aim of this study is to describe four patients with PFIC who underwent partial internal biliary diversion (PIBD)

Crossed testicular ectopia: Report of six cases

Crossed testicular ectopia or transverse testicular ectopia is an extremely rare anomaly characterised by migration of one testis towards the opposite inguinal canal, usually associated with unilateral inguinal hernia. This report describes six cases of crossed ectopic testes, one of the largest series, and with unusual clinical histories.Key words: Crossed testicular ectopia, transverse testicular ectopia, undescended Testi