Mucopolysaccharidosis IV A (Morquio syndrome A, MPS IVA) is a lysosomal storage disease caused by the deficiency of N-acetylgalactosamine-6-sulfatase (GALNS). The mutation spectrum in this condition is yet to be determined in Indians. We aimed to analyze the mutations in the GALNS gene in Asian Indians with MPS IVA. All the exons and the adjacent intronic regions of the gene were amplified and sequenced in sixty-eight unrelated Indian families. We identified 136 mutant alleles comprising of 40 different mutations. We report twenty-two novel mutations that comprise of seventeen missense (p.Asn32Thr, p.Leu36Arg, p.Pro52Leu, p.Pro77Ser, p.Cys79Arg, p.His142Pro, p.Tyr191Asp, p.Asn204Thr, p.Gly188Ser, p.Phe216Ser, p.Trp230Cys, p.Ala291Ser, p.Gly317Arg, p.His329Pro, p.Arg386Ser, p.Glu450Gly, p.Cys501Ser), three splice-site variants (c.120+1G>C, c.1003-3C>G, c.1139+1G>A), one nonsense mutation (p.Gln414*) and one frameshift mutation (p.Pro420Leufs*440). Eighteen mutations have been reported earlier. Among these p.Ser287Leu (8.82%), p.Phe216Ser (7.35%), p.Asn32Thr (6.61%) and p.Ala291Ser (5.88%) were the most frequent mutations in Indian patients but were rare in the mutational profiles reported in other populations. These results indicate that the Indian patients may have a distinct mutation spectrum compared to those of other populations. Mutant alleles in exon 1, 7 and 8 accounted for 44.8% of the mutations, and sequencing of these exons initially may be a cost-effective approach in Asian Indian patients. This is the largest study on molecular analysis of patients with MPS IVA reported in the literature, and the first report from India.

Multicentric osteolysis nodulosis and arthropathy (MONA) is an infrequently described autosomal recessive skeletal dysplasia characterized by progressive osteolysis and arthropathy. Inactivating mutations in MMP2, encoding matrix metalloproteinase-2, are known to cause this disorder. Fifteen families with mutations in MMP2 have been reported in literature. In this study we screened thirteen individuals from eleven families for MMP2 mutations and identified eight mutations (five novel and three known variants). We characterize the clinical, radiographic and molecular findings in all individuals with molecularly proven MONA from the present cohort and previous reports, and provide a comprehensive review of the MMP2 related disorders.

This is the first report of a founder EDAR mutation and of a significantly high frequency of autosomal recessive HED.

Background: Dysfunctional Uterine Bleeding (DUB) is the most common cause of abnormal uterine bleeding and is a major indication for referral to gynecological clinics. There are very few studies comparing the effect of ormeloxifene and progesterone in DUB. The objective of the study was to assess the efficacy and safety of Ormeloxifene in DUB and compare it with Norethisterone. Methods: Hundred women presenting with DUB were randomly allocated to 2 equal groups, Group-A, which received 60mg ormeloxifene twice a week for 12 weeks followed by 60mg once a week for next 12 weeks and Group-B, which received 5mg norethisterone twice daily for 21 days for 6 cycles. The primary outcomes were reduction in menstrual blood loss [measured by fall in PBAC (Pictorial Blood loss Assessment Chart) score and subjective assessment], rise in hemoglobin level and decrease in endometrial thickness. Results: The reduction in mean PBAC score with ormeloxifene (216 to 88) was significantly more than with norethisterone (262 to 162) at 3 months (p<0.01). The rise in hemoglobin concentration and fall in endometrial thickness were also significantly more with ormeloxifene than norethisterone (7.52g% to 9.2g% vs. 7.48g% to 8.4g%, p<0.05, and 12.12mm to 9.46mm vs. 12.05mm to 10.7mm, p<0.05, respectively). Further improvement at 6 months was much more with ormeloxifene. No major side effects were reported in any group. Conclusions: Both drugs are effective in treating DUB, but ormeloxifene is superior to norethisterone in reducing menstrual blood loss. [Int J Reprod Contracept Obstet Gynecol 2013; 2(2.000): 194-198

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