The hMSH2(M688R) Lynch syndrome mutation may function as a dominant negative

The hMSH2(M688R) Lynch syndrome mutation may function as a dominant negative.

The hMSH2(M688R) mismatch repair (MMR) gene mutation has been found in five large families from Tenerife, Spain, suggesting it is a Lynch syndrome or hereditary non-polyposis colorectal cancer (LS/HNPCC) founder mutation. In addition to classical LS/HNPCC tumors, these families present with a high incidence of central nervous system (CNS) tumors normally associated with Turcot or constitutional...

A dominant-negative GFI1B mutation in the gray platelet syndrome.

The gray platelet syndrome is a hereditary, usually autosomal recessive bleeding disorder caused by a deficiency of alpha granules in platelets. We detected a nonsense mutation in the gene encoding the transcription factor GFI1B (growth factor independent 1B) that causes autosomal dominant gray platelet syndrome. Both gray platelets and megakaryocytes had abnormal marker expression. In addition...

Identification of a dominant negative homeodomain mutation in Rieger syndrome.

Mutations in the PITX2 bicoid-like homeobox gene cause Rieger syndrome. Rieger syndrome is an autosomal-dominant human disorder characterized by glaucoma as well as dental hypoplasia, mild craniofacial dysmorphism, and umbilical stump abnormalities. PITX2 has also been implicated in the development of multiple organs and left-right asymmetry in the body plan. The PITX2 homeodomain has a lysine ...

Lynch syndrome: form, function, proteins, and basketball.

The Q188R mutation in human galactose-1-phosphate uridylyltransferase acts as a partial dominant negative.

A longstanding goal in the fields of molecular genetics and biochemistry has been to explain how naturally occurring mutations associated with human metabolic disease impair activity of the enzymes involved. This goal is particularly complex for enzymes composed of multiple subunits, because single mutations may exert both intra- and intersubunit effects on holoenzyme structure and function. We...