| #612004 | ||||||||||
| THROMBOCYTOPENIA 4; THC4 | ||||||||||
| Alternative titles; symbols | ||||||||||
| THROMBOCYTOPENIA, AUTOSOMAL DOMINANT, 4 | ||||||||||
| Phenotype Gene Relationships | ||||||||||
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| TEXT | ||||||||||
| A number sign (#) is used with this entry because of evidence that a form of autosomal dominant nonsyndromic thrombocytopenia is due to a mutation in cytochrome c (CYCS; 123970). For a phenotypic description and a discussion of genetic heterogeneity of thrombocytopenia, see 313900. | ||||||||||
| Clinical Features | ||||||||||
| Morison et al. (2008) described a 6-generation pedigree segregating autosomal dominant thrombocytopenia. Affected individuals had platelet counts ranging from 73 to 167 with a reference interval of 150 to 430. Clinical manifestations of thrombocytopenia were absent or mild. Affected individuals had normal longevity, fertility, and fitness with no evidence of neurodegenerative, muscular, eye, or kidney disease, or diabetes. | ||||||||||
| Molecular Genetics | ||||||||||
| Morison et al. (2008) identified a G-to-A transition at nucleotide 132 in exon 2 of the gene encoding cytochrome c (CYCS; 123970.0001) that caused a substitution of glycine by serine at codon 41 (G41S). Cytochrome c is a highly conserved protein, and glycine-41 is invariant among 113 eukaryotic species. Peripheral blood from affected family members contained the same proportion of immature platelets as controls, indicating no reduction of platelet life span. However, the absolute number of immature platelets was lower, suggesting reduced production. Bone marrow from a 76-year-old affected individual showed intramedullary naked megakaryocyte nuclei and platelets, suggesting dysregulated megakaryopoiesis with premature release of platelets into the marrow space rather than into sinusoids. | ||||||||||
| REFERENCES | ||||||||||
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