Genetic mapping of autosomal recessive microspherophakia to chromosome 14q24.3 in a consanguineous Pakistani family and screening of exon 36 of LTBP2 gene.

Latent transforming growth factor beta binding protein 2 (LTBP2) plays a critical role in the development of connective tissue structure and function. Mutations in gene encoding LTBP2 are known to cause syndromic and a non-syndromic microspherophakia. Here, we present a 'first' report of genetic linkage of microspherophakia (MSP) to LTBP2 locus in a large consanguineous Pakistani family with four affected individuals in three loops. Using polymorphic microsatellite markers, haplotypes and linkage analysis, the diseased phenotype in MSP001 family was mapped to the LTBP2 gene. A maximum two point Logarithm of the odds (LOD) score of 4.16 was obtained with marker D14S284 at θ =0. Mutational analysis of exon 36 of LTBP2 using Sanger's sequencing did not reveal any previously reported mutations. Further analysis of the remaining exons are required to identify the causative variant.

Comparison between Manual Traction, Manual Opening technique and Combination in Patients with cervical radiculopathy: Randomized Control Trial.

OBJECTIVE: To compare the effects of manual traction, manual intervertebral foramen opening technique and combination of the two techniques in patients with cervical radiculopathy. METHODS: The single-blind randomised control trial was conducted at Fauji Foundation Hospital, Rawalpindi, Pakistan, from July 2017 to January 2018, and comprised patients of either gender having unilateral upper extremity pain, paresthesia or numbness. The subjects were placed into groups I, II and III using sealed envelope method. Group I was treated with the opening of intervertebral foramen technique, while group II received manual traction of cervical spine, and group III received both techniques. Three sessions were conducted per week for 3 weeks. The outcome measures were neck disability index, Numeric pain rating scale, patient-specific functional scale, and range of motions of cervical spine. SPSS 21 was used for data analysis. RESULTS: Of the 40 patients, 17(30%) were males and 23(70%) were females. There were 13(32.5%)patients each in groups I and II, while group III had 14(35%). Mean age in group I was 42.41±6.86 years, in group II 40.95±7 .32 years and in group III 42.50±5.77 years. There was no statisticallysignificant difference among the three groups with respect to any parameter (p>0.05). Individual group analysis showed significant improvement (p<0.05) in all parameters . CONCLUSIONS: Manual intervertebral foramen opening technique, manual traction, and combination of both techniques were equally effective in decreasing pain, level of disability and improved cervical mobility in patients with cervical radiculopathy.

Mutational analysis of the CYP1B1 gene in Pakistani primary congenital glaucoma patients: Identification of four known and a novel causative variant at the 3' splice acceptor site of intron 2.

Primary congenital glaucoma (PCG) causes blindness in early age. It has an autosomal recessive pattern of inheritance, hence is more prevalent in populations with frequent consanguineous marriages that occur in the Pakistani population. Mutations in the CYP1B1 gene are commonly associated with PCG. The aim of the present study was to identify genetic mutations in the CYP1B1 gene in PCG cases belonging to 38 Pakistani families. DNA was extracted using blood samples collected from all enrolled patients, their available unaffected family members and controls. Direct sequencing of the CYP1B1 gene revealed a novel 3' splice acceptor site causative variant segregating in an autosomal recessive manner in a large consanguineous family with four PCG-affected individuals. The novel variant was not detected in 93 ethnically matched controls. Furthermore, four already reported mutations, including p.G61E, p.R355X, p.R368H, and p.R390H were also detected in patients belonging to nine different families. All identified causative variants were evaluated by computational programs, that is, SIFT, PolyPhen-2, and MutationTaster. Pathogenicity of the novel splice site variant identified in this study was analyzed by Human Splicing Finder and MaxEntScan. Ten out of 38 families with PCG had the disease due to CYP1B1 mutations, suggesting CYP1B1 was contributing to PCG in these Pakistani patients. Identification of this novel 3' splice acceptor site variant in intron 2 is the first report for the CYP1B1 gene contributing to genetic heterogeneity of disease.