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Background: Hereditary sensory and autonomic neuropathies (HSANs) are rare heterogeneous group of neurological disorders caused by peripheral nerve deterioration. The HSANs sub-clinical classes have clinical and genetic overlap which often lead to misdiagnosis. In the present study a Pakistani family with five affected members suffering from severe neuropathy were genetically analyzed to identify the disease causative element in the family. Methods: Genome wide high-density single nucleotide polymorphism (SNP) microarray analysis was carried out followed by whole exome sequencing of the affected proband and another affected sibling. Shared homozygous regions in all severely affected members were identified through homozygosity mapping approach. Results: The largest homozygous region of 14.1 Mb shared by the five severely affected members of the family was identified on chromosome 2. Subsequent exome sequencing identified a novel single nucleotide deletion c.2658del; p.(Ser887Profs*64) in KIF1A. Segregation analysis revealed that this mutation was homozygous in all five affected individuals of the family with severe clinical manifestation, while members of the family that were heterozygous carriers shared abnormal skin features (scaly skin) only with the homozygous affected members. Conclusions: A novel frameshift mutation p.(Ser887Profs*64) in KIF1A is the potential cause of severe HSANIIC in a Pakistani family along with incomplete penetrance in mutation carriers. We demonstrate that using a combination of different techniques not only strengthens the gene finding approach but also helps in proper sub-clinical characterization along with identification of mutated alleles exhibiting incomplete penetrance leading to intrafamilial clinical variability in HSAN group of inherited diseases. [ABSTRACT FROM AUTHOR]

Background: Giardia lamblia is a frequent cause of acute watery diarrhea and malabsorption in children in developing countries. Objective: To assess the frequency and associated factors of acute giardiasis in children admitted in tertiary care hospital with acute watery diarrhea. Methods: This cross sectional study was conducted in the department of Pediatrics, King Edward Medical University, Lahore from April to September 2018. Total of250 children of both genders, between 6 months to 12 years of age having acute watery diarrhea were included in this study by non-probability consecutive sampling. Children with acute dysentery, persistent diarrhea and children who already have received drugs (antibiotics, metronidazole) were excluded from the study. Fresh fecal sample were collected from every child and diagnosis of giardiasis was established by evidence of giardia by positive stool antigen by ELIZA. Data were entered in SPSS 22.0. Quantitative variables like age was presented as mean. Qualitative variables like gender were presented as frequency and percentages. Chi square test was applied to compare the children with and without acute giardiasis. The p-value < 0.05 was considered as significant. Results: Among 250 children of age between 6 months-12 years, presenting with acute watery diarrhea, 64 (25.6%) children had giardiasis. We found younger age (6-12 months) as an associated factor for giardiasis in children [p value 0.038, 1.578 (1.458-5.436)]. In this age group, 51.2% children had giardiasis. Gender of child, literacy level, socioeconomic status and area of residence of parents was not found to be the associated factor for acute giardiasis. Conclusion: We found that among children presenting with acute watery diarrhea, 25.6% cases had giardiasis. Younger age (6-12 months) was found to be associated factor for acute giardiasis in children. [ABSTRACT FROM AUTHOR]