Cost-effective Whole Exome Sequencing discovers pathogenic variant causing Neurofibromatosis type 1 in a family from Jammu and Kashmir, India.

Neurofibromatosis type 1 (NF1) is a multisystemic hereditary disorder associated with an increased risk of benign and malignant tumor formation predominantly on the skin, bone, and peripheral nervous system. It has been reported that out of all the NF1 cases, more than 95% cases develop the disease due to heterozygous loss-of-function variants in Neurofibromin (NF1) gene. However, identification of NF1 causative variants by presently recommended method of gene-targeted Sanger sequencing is challenging and cost-intensive due to the large size of the NF1gene with 60 exons spanning about 350 kb. Further, conducting the genetic studies is difficult in low resource regions and among families with the limited financial capabilities, restricting them from availing diagnostic as well as proper disease management measures. Here, we studied a three-generation family from Jammu and Kashmir state in India, with multiple affected family members showing clinical indications of NF1. We combinedly used two applications, Whole Exome Sequencing (WES) and Sanger sequencing, for this study and discovered a nonsense variant NM_000267.3:c.2041C>T (NP_000258.1:p.Arg681Ter*) in exon 18 of NF1 gene in a cost effective manner. In silico analyses further substantiated the pathogenicity of this novel variant. The study also emphasized on the role of Next Generation Sequencing (NGS) as a cost-effective method for the discovery of pathogenic variants in disorders with known phenotypes found in large sized candidate genes. The current study is the first study based on the genetic characterization of NF1 from Jammu and Kashmir-India, highlighting the importance of the described methodology adopted for the identification and understanding of the disease in low resource region. The early diagnosis of genetic disorders would open the door to appropriate genetic counseling, reducing the disease burden in the affected families and the general population at large.

Inbreeding as a cause for deafness: Dadhkai study.

BACKGROUND: We report on the higher prevalence of deaf-mutes from a village in Jammu and Kashmir State of India. MATERIALS AND METHODS: A cross-sectional study among 79 deaf mutes using pedigree analysis, audiometry, imaging and molecular analysis. RESULTS: A high rate of hereditary deafness with 79 individuals diagnosed to be suffering from non-syndrome deafness in a total population of 2452 individuals residing in the village. INTERPRETATION: Flourishing of intermarriages led to a population with high prevalence of deafness.

Prevalence of dementia among Kashmiri migrants.

BACKGROUND: Neurological diseases are common disorders resulting in the loss of productive life and disability. Dementia is becoming a major public health problem in the developing world also. AIM: To ascertain the prevalence of dementia among Kashmiri Pandit population aged 60 years and above. MATERIALS AND METHODS: A cross-sectional survey was conducted among the elderly population of the Kashmiris living in a migrant camp. We developed and used a Kashmiri version of the Mini-Mental State Examination as the test instrument, and a score below 24 was considered indicative of dementia. A functional ability questionnaire was also administered to the subjects. A neurologist carried out the examinations. RESULTS: A sample comprising 200 subjects (95 males and 105 females) were evaluated. The prevalence of dementia is 6.5% among the Kashmiri Pandit population aged 60 years and above, which is higher than that reported from other parts of India.

Diagnosis of intraventricular cysticercosis by magnetic resonance imaging: improved detection with three-dimensional spoiled gradient recalled echo sequences.

Neurocysticercosis (NCC) is caused when the cysticercus larvae of Taenia solium infect the central nervous system. The larvae usually land in the parenchymal tissue, but quite rarely can lodge in the ventricles and cisterns of the brain. Unlike parenchymal NCC, it is not easy to demonstrate the cysticercus cysts within the cerebrospinal fluid spaces. Computed tomography and even conventional MR sequences can fail to detect such cysts. However, obtaining three-dimensional spoiled gradient recalled echo imaging sequences can help in improving the detection of intraventricular NCC, as is borne out by a case described in the present report. The use of such special MR sequences is therefore strongly advocated in suspected cases of intraventricular NCC.