MYH9

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Human chromosome 22 idiogram. MYH9 is located on tape q11.2

MYH9 ( myosin, heavy chain 9 ) is a gene that is located in humans on chromosome 22 gene locus q11.2.

Syndromes and abnormalities associated with MYH9

Point mutations in MYH9 are four very rare autosomal - dominant inherited diseases responsible:

The May-Hegglin anomaly is the most common form of these extremely rare diseases.

The four syndromes associated with point mutations in MYH9 differ in the location of the point mutation, which in turn leads to different symptoms :

Syndrome / abnormality Macrothrombocytopenia Leukocyte inclusions Glomerulonephritis Hearing impairment Cataract
May Hegglin Anomaly (MHA) + + - - -
Sebastian Syndrome (SBS) + + - - -
Epstein Syndrome (EPS) + - + + -
Fechtner Syndrome (FTNS) + + + + +

Macrothrombocytopenia is characterized by a lack of platelets (called thrombocytopenia ) and oversized platelets.

Particularly in people of black African descent, single nucleotide polymorphisms of MYH9 are associated with an unfavorable prognosis for nephrosclerosis and focal segmental glomerulosclerosis . MYH9 itself is probably not responsible for the increased risk, but rather the directly neighboring gene APOL1. Variants of this gene give the carriers a resistance to infections with Trypanosoma brucei rhodesiense and thus a selection advantage . The gene APOL1 encodes for the protein apolipoprotein LI (APOL1), which was found only in humans and gorillas. When trypanosomes ingest APOL1 through endocytosis , APOL1 forms pores in the membrane of the lysosomes , which lead to lysis of the parasite cells. The pathomechanism by which APOL1 leads to kidney damage in humans is not yet known.

Genetics and Construction

The MHY9 gene codes for the heavy chain of a non-muscle myosin type IIA (NMMHC-IIA). This protein is in some blood cells, including monocytes and platelets , in the cochlea ( cochlear ) and in the kidneys expressed .

The human MYH9 gene, like the murine , contains 41 exons . The murine NMMHC-IIA protein encoded by the MYH9 gene consists of 1960 amino acids and is 98% identical to human.

literature

Web links

Individual evidence

  1. ↑ UCSC Genome Browser on Human Mar. 2006 Assembly: chr22: 35,007,273-35,113,958
  2. ↑ Human Gene MYH9 (uc003apg.1) Description and Page Index . genome.ucsc.edu
  3. ↑ JA Martignetti et al .: The gene for May-Hegglin anomaly localizes to a <1-Mb region on chromosome 22q12.3-13.1. In: Am J Hum Genet. 66/2000, pp. 1449-1454. PMID 10739770 .
  4. ↑ M. Picu et al.: An 8-Year-Old Girl With Thrombocytopenia . In: Archives of Pathology & Laboratory Medicine . Volume 129, 2005, pp. 214-217. PMID 16329740 .
  5. ↑ KE Heath et al.: Nonmuscle myosin heavy chain IIA mutations define a spectrum of autosomal dominant macrothrombocytopenias: May-Hegglin anomaly and Fechtner, Sebastian, Epstein, and Alport-like syndromes. In: Am J Hum Genet. 69/2001, pp. 1033-1045. PMID 11590545 .
  6. ^ WH Linda Kao et al: MYH9 is associated with nondiabetic end-stage renal disease in African Americans . In: Nature Genetics . tape 40 , no. 10 , October 2008, p. 1185-1192 , doi : 10.1038 / ng.232 , PMID 18794854 .
  7. ↑ Jeffrey B Kopp et al .: MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis . In: Nature Genetics . tape 40 , no. 10 , October 2008, p. 1175-1184 , doi : 10.1038 / ng.226 , PMID 18794856 .
  8. ^ Giulio Genovese et al: Association of trypanolytic ApoL1 variants with kidney disease in African Americans . In: Science . tape 329 , no. 5993 , August 13, 2010, p. 841-845 , doi : 10.1126 / science.1193032 , PMID 20647424 .
  9. ↑ E. Pays, B. Vanhollebeke, L. Vanhamme, F. Paturiaux-Hanocq, DP Nolan, D. Pérez-Morga: The trypanolytic factor of human serum. In: Nat Rev Microbiol . 4 (6), Jun 2006, pp. 477-486. PMID 16710327 .
  10. ↑ M. D'Apolito et al .: Cloning of the murine non-muscle myosin heavy chain IIA gene ortholog of human MYH9 responsible for May-Hegglin, Sebastian, Fechtner, and Epstein syndromes. In: Genes. 286/2002, pp. 215-222. PMID 11943476 .