The microbiota and immune-mediated diseases: Opportunities for therapeutic intervention.

A multitude of diverse microorganisms, termed the microbiota, reside in the gut, respiratory tract, skin, and genital tract of humans and other animals. Recent advances in metagenomic sequencing and bioinformatics have enabled detailed characterization of these vital microbial communities. Studies in animal models have uncovered vital previously unrecognized roles for the microbiota in normal function of the immune responses, and when perturbed, in the pathogenesis of diseases of the gastrointestinal tract and lungs, but also at distant sites in the body including the brain.

A novel 800 kb microduplication of chromosome 16q22.1 resulting in learning disability and epilepsy may explain phenotypic variability in a family with 15q13 microdeletion.

The phenotype of 15q13.3 microdeletion is variable and can be non-penetrant. Recently, "second-hit hypothesis" has been proposed as a possible explanation for some variability in recurrent microdeletion syndromes.

Haploinsufficiency of the nerve growth factor beta gene in a 1p13 deleted female child with an insensitivity to pain.

Pain insensitivity is mediated at the genetic level by the disruption of specific genes associated with neuronal development. Mammalian in vivo and in vitro studies have shown the nerve growth factor (NGF) gene to play an integral role in nerve maintenance and function. Pain insensitivity in humans can be attributed to hereditary sensory and autonomic neuropathies (HSAN) of which there are five classes (HSAN I - HSAN V).