Search

Multiple congenital anomalies-hypotonia-seizures syndrome 3 (MCAHS3) is caused by genetic defects in glycosyl-phosphatidylinositol transamidase complex synthesis due to mutations in the PIGT gene. The disease encompasses dysmorphism, cardiac, genito-urinary and skeletal anomalies, developmental delay and epilepsy in variable severity. Only 39 such cases have been reported till date in literature. We reported the first Indian case with neonatal presentation and overall the sixth case of MCAHS3 to present in neonatal age. The pro-band was a male baby born to non-consanguineous parents. He had perinatal depression, craniofacial dysmorphism, epileptic encephalopathy, left radio-ulnar congenital fractures and respiratory failure managed with multiple anti-epileptics, invasive ventilation and limb splinting. Clinical exome sequencing revealed an autosomal recessive homozygous PIGT gene mutation on exon 6 of chromosome 20 with a variant nomenclature of C.709G>C with heterozygous parents confirming MCAHS3. This report expands the range of information available on MCAHS3. It highlights the need to elaborately investigate dysmorphic newborns with severe hypotonia along with the described neurological symptoms, so as to pin point this potentially diagnosable entity.

The liver flukes Fasciola hepatica and F. gigantica infect livestock worldwide and threaten food security with climate change and problematic control measures spreading disease. Fascioliasis is also a foodborne disease with up to 17 million humans infected. In the absence of vaccines, treatment depends on triclabendazole (TCBZ), and overuse has led to widespread resistance, compromising future TCBZ control. Reductionist biology from many laboratories has predicted new therapeutic targets. To this end, the fatty-acid-binding protein (FABP) superfamily has proposed multifunctional roles, including functions intersecting vaccine and drug therapy, such as immune modulation and anthelmintic sequestration. Research is hindered by a lack of understanding of the full FABP superfamily complement. Although discovery studies predicted FABPs as promising vaccine candidates, it is unclear if uncharacterized FABPs are more relevant for vaccine formulations. We have coupled genome, transcriptome, and EST data mining with proteomics and phylogenetics to reveal a liver fluke FABP superfamily of seven clades: previously identified clades I-III and newly identified clades IV-VII. All new clade FABPs were analyzed using bioinformatics and cloned from both liver flukes. The extended FABP data set will provide new study tools to research the role of FABPs in parasite biology and as therapy targets.