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We report a 29 week fetus with arthrogryposis multiplex congenita, multiple joint dislocations, scoliosis and dysmorphism who was detected to be double heterozygote for putatively pathogenic FBN1 (NM_000138.4:c.6004C > T; p.Pro2002Ser) and FBN2 (NM_001999.3:c.2945G > T; p.Cys982Phe) variants on exome sequencing. The de-novo status of these variants is not confirmed as parental genotypes could not be ascertained. A comparison of the post-mortem findings of the fetus with reported phenotypes of Beals and Marfan syndromes indicated overlapping clinical features suggestive of a blended phenotype.

Disruption of the initiation of DNA replication is significantly associated with Meier-Gorlin syndrome (MGORS), an autosomal recessive condition of reduced growth, microtia and patellar a/hypoplasia. Biallelic mutations in CDC45, a member of the pre-initiation complex in DNA replication, cause a spectrum of phenotypes ranging from MGORS with craniosynostosis, through to isolated short stature and craniosynostosis. Here we report two affected sibs with MGORS and craniosynostosis, with biallelic variants in CDC45 identified by 10X Chromium whole genome sequencing. One variant is a frameshift mutation, predicted to be pathogenic, and is inherited in trans with a synonymous variant in a non-canonical exon (exon 7) of CDC45. An in vitro splicing assay showed that while the canonical CDC45 exon 6-exon 8 transcript (with skipping of exon 7; numbering as per NM001178010.2) remained as the predominant transcript, the variant allele induced the use of novel splice acceptor sites in intron 6, all of which produced transcripts harbouring premature stop codons. This perturbation of canonical splicing provides evidence that this synonymous variant is indeed a deleterious alteration in this family. This report adds to the initial patient cohort in which several synonymous variants were also described, further highlighting the contribution of this variant type in CDC45. It also reiterates the true potential pathogenicity of synonymous variants, which is a mutation type that is commonly ignored in variant prioritization strategies.

Band like calcification with simplified gyration and polymicrogyria (BLC-PMG) is a distinct neuroradiological phenotype initially reported as a pseudo-TORCH syndrome and known to result from biallelic mutations in the Occludin(OCLN) gene. This is report of a family of Indian origin with two affected sibs and segregation of a homozygous novel OCLN mutation in the exon 3(NG_028291.1(OCLN_v001):c.252delC). A literature review suggests that renal dysfunction may be an unrecognized phenotypic manifestation of OCLN mutations and monitoring for the same should form part of the clinical care of these individuals.

GM1 gangliosidosis is a lysosomal storage disorder caused by mutations in the GLB1 gene, leading to the deficiency of the enzyme β-d-galactosidase. In this study, we report molecular findings in 50 Asian Indian families with GM1 gangliosidosis. We sequenced all the exons and flanking intronic sequences of GLB1 gene. We identified 33 different mutations (20 novel and 13 previously reported). The novel mutations include 12 missense (p.M1?, p.E129Q, p.G134R, p.L236P, p.G262E, p.L297F, p.Y331C, p.G414V, p.K493N, p.L514P, p.P597L, p.T600I), four splicing (c.246-2A>G, c.397-2A>G, c.552+1G>T, c.956-2A>G), three indels (p.R22Qfs*8, p.L24Cfs*47, p.I489Qfs*4) and one nonsense mutation (p.Q452*). Most common mutations identified in this study were c.75+2InsT (14%) and p.L337P (10%). Known mutations accounted for 67% of allele frequency in our cohort of patients, suggesting that these mutations in GLB1 are recurrent across different populations. Twenty three mutations were localized in the TIM barrel domain, β-domain 1 and β-domain 2. In silico sequence and structure analysis of GLB1 reveal that all the novel mutations affect the function and structure of the protein. We hereby report on the largest series of patients with GM1 gangliosidosis and the first from India.

Summary The TRAM flap, DIEP flap, and gluteal free flaps are routinely used for breast reconstruction. However, these have seldom been described for reconstruction of buttock deformities. We present three cases of free flaps used to restore significant buttock contour deformities. They introduce vascularised bulky tissue and provide adequate cushioning for future sitting, as well as correction of the aesthetic defect.

Electrical switchboards are devices, involving an assembly of panels and switches, that distribute electricity from one source to another. They are most commonly found in industrial or commercial settings where large amounts of electrical current are required. Inside the switchboard there is a bank of wide copper strips called busbars to which the switchgear is connected. PURPOSE: To document the incidence and outcome of flash burns due to electrical switchboard explosions presenting to Concord Hospital Burns Unit, from January 2000 to December 2008. METHODS: The Concord Hospital Burns Unit Database was reviewed for admissions due to electrical burns from January 2000 to December 2008. RESULTS: There were 119 electrical burns admitted during the study period, 20 of which were due to high voltage current. Ninety-nine others were low voltage injuries and included 37 cases of electrical burns due to low voltage electrical switchboard explosions. All of the electrical switchboard burns occurred in male electricians. Twenty-one of the 37 low voltage injuries required admission and 7 of them required skin grafting. The mean LOS was 9.95 days. Twenty cases suffered serious complications including major psychological problems and ocular injuries. CONCLUSIONS: Flash burns resulting from switchboard explosions account for a significant proportion of all electrical burns presenting to our institution. These burns may highlight deficits in taking safety precautions and the use of personal protection equipment. Despite the small area of injury the long term psychological sequelae were significant resulting in a delayed return to employment, and there was a high incidence of eye injuries. Additional efforts are therefore required towards the prevention of such injuries. Language: en

The association of four common polymorphisms of vascular endothelial growth factors (VEGF) with recurrent miscarriages (RM) was evaluated in North Indian women for 200 patients with RM and 200 controls. The subjects were genotyped for the polymorphisms −2578C/A, −2549 18-bp I/D, −1154G/A and +936C/T. Association of VEGF genotypes, alleles and haplotypes with recurrent miscarriage were evaluated by Fisher's exact test. −1154G/A and +936C/T modified the risk of RM. The −1154A allel and +936T allel significantly increased the risk of RM (OR=1.485, P =0.0210, 95% CI 1.072–2.057 and OR=1.869, P =0.0054, 95% CI 1.214–2.876 respectively). Risk was further increased when –1154A/A genotype and +936C/T genotype were considered (OR=2.0, P =0.0310, 95% CI 1.068–3.747 and OR=1.716, P =0.0293, 95% CI 1.058–2.784 respectively). However, no association was found between −2578C/A or −2549 18-bp I/D and RM. Four haplotypes, AIAC, ADAC, CIAT and ADGT, were found to predispose to RM while the haplotypes CIAC, CDGT and ADGC were found to show protective effect. In conclusion, two common polymorphisms of the VEGF gene, −1154G/A and +936C/T, increase the risk of RM in North Indian women. RM is also predisposed in the presence of haplotypes AIAC, ADAC, CIAT and ADGT. In many of the women with three or more miscarriages, no definite cause for their illness can be found. Recently researchers have found that a growth factor which promotes the growth of blood vessels known as vascular endothelial growth factor (VEGF) plays an important role in the formation of blood supply of the fetus through the placenta. Reduced concentrations of this factor might contribute to the improper formation of the placenta, which may cause recurrent miscarriage. The gene for VEGF is polymorphic consisting of variations in its nucleotide sequence at various locations. Researchers have shown that these variations in the gene lead to different concentrations of VEGF in different people. Hence, there may be some women with a certain polymorphism(s) who have lower VEGF production and so are at risk of recurrent miscarriage. In this study conducted in North India, we tested these polymorphisms in women with and without recurrent miscarriage and tried to find if any particular polymorphism increased the probability of a woman having a recurrent miscarriage. We found that at least two polymorphisms of the VEGF gene, −1154 G/A and +936C/T, did increase the risk of recurrent miscarriage among carriers of the uncommon allele.