Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II.

Mucopolysaccharidoses (MPS), a subgroup of lysosomal storage disorders, are caused due to deficiency of specific lysosomal enzyme involved in catabolism of glycosaminoglycans. To date more than 200 pathogenic variants in the alpha-l-iduronidase (IDUA) for MPS I and ∼500 pathogenic variants in the iduronate-2-sulphatase (IDS) for MPS II have been reported worldwide. The mutation spectrum of MPS type I and MPS type II disorders in Indian population is not characterized yet. In this study, we carried out clinical, biochemical, molecular and in silico analyses to establish the mutation spectrum of MPS I and MPS II in the Indian population. We conducted molecular analysis for 60 MPS-affected patients [MPS I (n = 30) (Hurler syndrome = 17, Hurler-Scheie syndrome = 13), and MPS II (n = 30) (severe = 18, attenuated = 12)] and identified a total of 44 [MPS I (n = 22) and MPS II (n = 22)] different pathogenic variants comprising missense, nonsense, frameshift, gross deletions and splice site variants. A total of 20 [MPS I (n = 14), and MPS II (n = 6)] novel pathogenic sequence variants were identified in our patient cohort. We found that 32% of pathogenic variants detected in IDUA were recurrent and 25% in MPS II. This is the first study revealing the mutation spectrum of MPS I and MPS II patients in the Indian population.

Phenotypic and molecular characterization of partial trisomy 2q resulting from insertion-duplication in chromosome 18q: a case report and review of literature.

Trisomy 2q is a well-documented chromosomal anomaly with considerable variation in the phenotype depending upon the breakpoints and the co-existing chromosomal aberrations. The case of a dysmorphic male infant found to have trisomy of the 2q31.1-q37.3 segment, resulting from insertion-duplication of this segment in chromosome 18q23 is reported here. The rearrangement was resolved in detail by cytogenetic microarray and whole chromosome paint-based fluorescence in situ hybridization studies. There is some overlap of the phenotypic features in the reported patient with those described in previously reported cases with partial trisomy 2q. A detailed review of the available literature on 2q trisomy has also been presented and delineation of the phenotypic characteristics common to all patients with 2q trisomy has been attempted.

Role of non-HLA genetic variants in end-stage renal disease.

Cytokines and intercellular adhesion molecule (ICAM) play a crucial role in the pathogenesis of primary kidney disease and progression to end-stage renal disease (ESRD). Cytokine secretion is reported to be dependent on the single nucleotide polymorphisms located in the cytokine genes. The role of different polymorphisms in cytokines and ICAM genes as probable susceptibility factors for ESRD has been explored in the present study. The study was conducted on 258 ESRD patients and on ethnically matched 569 controls. Individuals were genotyped for interleukin (IL)-6 (G174C), IL-4 (C590T), tumor necrosis factor-alpha (TNF-alpha) (-G308A and -G238A) and ICAM-1 (A469G) gene polymorphisms using standard polymerase chain reaction-restriction fragment length polymorphism-based method. We observed significant difference in the genotype frequencies of the TNF-alpha-308AA [P = 0.001; odds ratios (OR) = 7.61, 95% confidence intervals (CI) = 2.1-27.9] and TNF-alpha-238AA (P = 0.001; OR = 5.8, 95% CI = 2.2-15.1). Furthermore, C allele of IL-6 -G174C and G allele of ICAM-1 A469G were significantly different in ESRD patients when compared with controls (P = 0.0001; OR = 5.5, 95% CI = 3.9-7.7 and P < 0.0001; OR = 3.8, 95% CI = 3.1-4.7). For the IL-4 C590T polymorphism, although the homozygous mutant genotype (TT) was not found to be significantly associated with ESRD, a statistically significant association with T allele (P = 0.008) was observed. Furthermore, combined analysis showed a higher risk in ESRD patients with high IL-4- and low IL-6-producing genotypes, low IL-4- and low IL-6-producing genotypes and high-producing genotype of TNF-alpha (308 and 238) with the increased risk of 6.47-, 3.7- and 3.3-fold, respectively. Our results suggest that IL-6, IL-4, TNF-alpha and ICAM gene polymorphisms are implicated in ESRD.

Multiple sclerosis in Oman.

OBJECTIVE: To describe the clinical characteristics of multiple sclerosis (MS) seen in Oman and compare it with those seen in the Arabian peninsula, the rest of Asia and the Western world. METHODS: A hospital based case descriptive study of MS patients, seen at Sultan Qaboos University Hospital in the Sultanate of Oman, between June 1990- June 2000. RESULTS: We saw a total of 30 patients during the study period, with a prevalence of 4/100,000. Mean age at onset was 27 and male to female ratio was 1.1:1. Visual and motor symptoms were the most common presenting features. Lesions were distributed in the optic nerve in 17, spinal cord in 16, cerebral hemispheres in 12 and brain stem and cerebellum in 10. One third of patients had the optico-spinal form of the disease. Twenty-three patients had a remitting and relapsing course, 4 had secondary progressive and 3 had a primary progressive course. Cerebrospinal fluid oligoclonal band was positive only in 20% of patients, and we carried out HLA analysis in 24 of these patients. CONCLUSION: The incidence of MS is low in Oman, but similar to other countries in the region. The optico-spinal form of the disease constituted 30% in this series, comparable to other series reported from Asia. Generally, the clinical profile of MS seen in Oman is very similar to those reported from the Arabian Peninsula and other Asian regions.