Asparagine synthetase deficiency is a rare inborn error of metabolism caused by a defect in ASNS, a gene encoding asparagine synthetase. It manifests with a severe neurological phenotype manifesting as severe developmental delay, congenital microcephaly, spasticity and refractory seizures. To date, nineteen patients from twelve unrelated families have been identified. Majority of the mutations are missense and nonsense mutations in homozygous or compound heterozygous state. We add another case from India which harbored a novel homozygous missense variation in exon 11 and compare the current case with previously reported cases.

Autosomal recessive spastic ataxia of Charlevoix‐Saguenay (ARSACS) was described by Bouchard and colleagues in 1978 from Quebec, Canada, as a rare cause of autosomal recessive cerebellar ataxia. 1.2 Subsequent reports confirmed the presence of this condition in other parts of the world, including Europe and, in Asia, Japan.3 Although mutations in the sacsin molecular chaperone gene (SACS) were also identified during a recent mass exome sequencing study of Indian families with ataxia,4 there is no detailed clinical and imaging report of a genetically proven individual with ARSACS from India. We report a patient from the western Indian state of Maharashtra in whom typical clinical and especially imaging features aroused high suspicion of ARSACS, prompting targeted SACS gene testing and, subsequently, the discovery of a novel pathogenic SACS duplication.

Muthusamy B, Selvan LDN, Nguyen TT, Manoj J, Stawiski EW, Jaiswal BS, Wang W, Raja R, Ramprasad VL, Gupta R, Murugan S, Kadandale JS, Prasad TSK, Reddy K, Peterson A, Pandey A, Seshagiri S, Girimaji SC, Gowda H, OMICS, 2017 May;21(5):295-303. Robust diagnostics for many human genetic disorders are much needed in the pursuit of global personalized medicine. Next- generation sequencing now offers new promise for biomarker and diagnostic discovery, in developed as well as resource-limited countries. In this broader global health context, X-linked intellectual disability (XLID) is an inherited genetic disorder that is associated with a range of phenotypes impacting societies in both developed and developing countries. Although intellectual disability arises due to diverse causes, a substantial proportion is caused by genomic alterations. Studies have identified causal XLID genomic alterations in more than 100 protein-coding genes located on the X-chromosome. However, the causes for a substantial number of intellectual disability and associated phenotypes still remain unknown. Identification of causative genes and novel mutations will help in early diagnosis as well as genetic counseling of families. Advent of next-generation sequencing methods has accelerated the discovery of new genes involved in mental health disorders. In this study, we analyzed the exomes of three families from India with nonsyndromic XLID comprising seven affected individuals. The affected individuals had varying degrees of intellectual disability, microcephaly, and delayed motor and language milestones. We identified potential causal variants in three XLID genes, including PAK3 (V294M), CASK (complex structural variant), and MECP2 (P354T). Our findings reported in this study extend the spectrum of mutations and phenotypes associated with XLID, and calls for further studies of intellectual disability and mental health disorders with use of next-generation sequencing technologies.

Robust diagnostics for many human genetic disorders are much needed in the pursuit of global personalized medicine. Next-generation sequencing now offers new promise for biomarker and diagnostic discovery, in developed as well as resource-limited countries. In this broader global health context, X-linked intellectual disability (XLID) is an inherited genetic disorder that is associated with a range of phenotypes impacting societies in both developed and developing countries. Although intellectual disability arises due to diverse causes, a substantial proportion is caused by genomic alterations. Studies have identified causal XLID genomic alterations in more than 100 protein-coding genes located on the X-chromosome. However, the causes for a substantial number of intellectual disability and associated phenotypes still remain unknown. Identification of causative genes and novel mutations will help in early diagnosis as well as genetic counseling of families. Advent of next-generation sequencing methods has accelerated the discovery of new genes involved in mental health disorders. In this study, we analyzed the exomes of three families from India with nonsyndromic XLID comprising seven affected individuals. The affected individuals had varying degrees of intellectual disability, microcephaly, and delayed motor and language milestones. We identified potential causal variants in three XLID genes, including PAK3 (V294M), CASK (complex structural variant), and MECP2 (P354T). Our findings reported in this study extend the spectrum of mutations and phenotypes associated with XLID, and calls for further studies of intellectual disability and mental health disorders with use of next-generation sequencing technologies.

We tested 3 ild Asian elephants (Elephas maximus) in southern India and confirmed infection in 3 animals with Mycobacterium tuberculosis, an obligate human pathogen, by PCR and genetic sequencing. Our results indicate that tuberculosis may be spilling over from humans (reverse zoonosis) and emerging in wild elephants.

EGFR (epidermal growth factor receptor) is important for the proliferation of stem cells across the body including the hematopoietic niche. However, the role of EGFR in aplastic anemia and subsequent responses to standard-of-care therapy is unknown.TWIST is a basic helix-loop-helix transcription factor recently found to regulate the hematopoietic stem cell (HSC) niche. The HSC niche is important for treatment of aplastic anemia. Telomerase and associated gene mutations have been reported in aplastic anemia, but these mutations are not present in all subjects and hence the cellular mechanisms of therapeutic responses observed is not explained by deregulated telomerase or associated genes.

Manitoba-oculo-tricho-anal (MOTA) syndrome is very rare syndrome characterized by aberrant hairline, eye anomalies (ocular hypertelorism, cryptophthalmos, and upper eyelid colobomas), bifid nose, omphalocele and anorectal anomalies. MOTA syndrome was first reported in 1992 in Oji-cree community from the Island Lake region of Manitoba, Canada. Till date very few cases of MOTA have been reported and none from India. We report first case of MOTA syndrome from India. A two month old male baby was brought with complaints of defect in right upper eye lid since birth. He was the second born child of a second degree consanguineously married couple at 37 weeks of gestation. On physical examination, the baby had right upper eyelid coloboma, ocular hypertelorism, bifid nose, small nasal ala and bilateral undescended testis. Investigations revealed high anorectal anomaly and right renal agenesis. Whole exome sequencing showed homozygous nonsense variation in exon 25 of the FREM1 gene that resulted in a stop codon. This case gains importance as it is the first case of MOTA being reported from India and bilateral undescended testis which was seen this case is an addition to the variable clinical spectrum of MOTA.

We report on a sib pair of Indian origin presenting with intellectual disability, dysmorphism, and macrocephaly. Exome sequencing revealed a homozygous splice site HERC1 mutation in both probands. Functional analysis revealed use of an alternate splice site resulting in formation of a downstream stop codon and nonsense mediated decay. In the light of recent reports of HERC1 mutations in two families with a similar phenotypic presentation, this report reiterates the pathogenic nature and clinical consequences of HERC1 disruption.

Background:Fluid flow plays an important role in vascular development. However, the detailed mechanisms, particularly the link between flow and modulation of gene expression during vascular development, remain unexplored. In chick embryo, the key events of vascular development from initiation of heart beat to establishment of effective blood flow occur between the stages HH10 and HH13. Therefore, we propose a novel in vivo model to study the flow experienced by developing endothelium. Objective:Using this model, we aimed to capture the transcriptome dynamics of the pre- and post-flow conditions. Methods:RNA was isolated from extra embryonic area vasculosa (EE-AV) pooled from three chick embryos between HH10–HH13 and RNA sequencing was performed. Results:The whole transcriptome sequencing of chick identified up-regulation of some of the previously well-known mechanosensitive genes including NFR2, HAND1, CTGF and KDR. GO analyses of the up-regulated genes revealed enrichment of several biological processes including heart development, extracellular matrix organization, cell-matrix adhesion, cell migration, blood vessel development, patterning of blood vessels, collagen fibril organization. Genes encoding for gap junctions proteins which are involved in vascular remodeling and arterial–venous differentiation, and genes involved in cell–cell adhesion, and ECM interactions were significantly up-regulated. Validation of selected genes through semi quantitative PCR was performed. Conclusion:The study indicates that shear stress plays a major role in development. Through appropriate validation, this platform can serve as an in vivo model to study conditions of disturbed flow in pathology as well as normal flow during development.