Oh, this one looks good: #201250 ACROMESOMELIC DYSPLASIA, HUNTER-THOMPSON TYPE. Maybe this will be the gene associated with confrontational writing skills and the ability to ingest copious quantities of illicit drugs.
But alas no. Acromesomelic Dysplasia, Hunter-Thompson type, a.k.a. AMDH or Acromesomelic dwarfism, is a rare autosomal recessive form of dwarfism first identified by Hunter and Thompson back in 1976.. The phenotype of the disease is characterized by shortened limbs, small hands and feet, and an average height of only 120 cm. A whole host of skeletal defects accompany this disease as well. Langer et al. (1989) published a paper in Human Genetics describing the AMDH phenotype while comparing it to another kind of dwarfism called Grebe chondrodysplasia. They published these pictures showing the shortened limbs, hands and feet of Hunter-Thompson type and Grebe-type dwarfisms. The two youngsters are examples of the Hunter-Thompson phenotype, while the older woman suffers from Grebe-type chondrodysplasia.
As it turns out, both types of dwarfism result from mutations in the same gene - GROWTH/DIFFERENTIATION FACTOR 5; GDF5.This gene codes for a secreted growth factor related to the Bone Morphogenic protein (BMP) family. These proteins are very important signaling molecules that mediate all kinds of developmental processes. It's a small world, because some members of my lab, in collaboration with another lab, just published a paper about GDF5's sister gene, GDF6. Cool, I learned something relevant today! Anyways, mutations in GDF5 are responsible for a whole host of diseases in humans. Thomas et al. (1996) were the first to show that a mutation in GDF5 (then called CDMP1) was responsible for Hunter/Thompson type dwarfism. Specifically, AMDH patients have a 22 base-pair tandem duplication in the GDF5 gene that causes a frameshift mutation. As a result, 43 of the 120 amino acids in the secreted form of GDF5 bear no resemblance to the normal protein, and obviously this disrupts its function. I think it's really cool that every disease associated with GDF5 is as a result of unique mutations within the GDF5 gene. For example, the Grebe-type phenotype results from a single amino acid change - cysteine 400 to tyrosine. This mutation creates a dominant negative form of the protein, meaning that the mutated GDF5 actually prevents other BMPs from getting secreted from the cell. This probably accounts for the more severe phenotype of Grebe-type chondrodysplasia compared to Hunter/Thompson-type.
Thus ends the first installment of the Gene Genie. Wow, this was fun! I think I'll enjoy this...
