Haploinsufficiency

For some of the GLUT isotypes, the phenotype of null mutants is known. Haploinsufficiency of the GLUT1 in... 

SUMOl haploinsufficiency has been linlced to a developmental defect Based on the finding that a patient with a cleft lip and palate had a mutation in the SUMOl gene locus, a mouse model was generated that had reduced SUMOl expression. Increased frequency for a cleft palate or oblique facial cleft was observed in the transgenic mice, suggesting that SUMO haploinsufficiency can lead to developmental defects. 

Song, W., Sullivan, M., Legate, R., Hutchings, S., Tan, X., Kufrin, D., Ratajczak, J., Resende, L, Haworth, C., Hock, R., et al. (1999) Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukemia. Nat Genet 23, 166-175. 

Sun, W. and Downing, J. (2004) Haploinsufficiency of AMLl results in a decrease in the number of LTR-HSCs while simultaneously inducing an increase in more mature progenitors. Blood 104, 3565-3572. 

Haploinsufficiency, or when 50% of normal gene activity is inadequate a-Thalassemia trait and the a-globin gene P-Thalassemia trait and the P-globin gene... 

Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2. Nat Genet 33 192-196. 

Prasad, V., Boivin, G. P., Miller, M. L., Liu, L. H., Erwin, C. R., Warner, B. W., and Shull, G. E., 2005, Haploinsufficiency of Atp2a2, encoding the sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 Ca2+ pump, predisposes mice to squamous cell tumors via a novel mode of cancer susceptibility. Cancer Res, 65 8655-61. 

Haploinsufficiency of human SPCA1 results in Hailey-Hailey disease (HHD) (Hu et al., 2000 Sudbrak et al., 2000), which highlights the critical role of this housekeeping Ca2+ and Mn2+ pump in cellular ion homeostasis. We will review the properties of this mutated SPCA1 and discuss how SPCA1 contributes to the physiology of the normal skin. 

G Giaever, D Shoemaker, TW Jones, H Liang, EA Winzler, A Astromoff, RW Davis. Genomic profiling of drug sensitivities via induced haploinsufficiency. Nature Genet 21 278-283, 1999. 

Kurotaki N, Imaizumi K, Harada N et al (2002) Haploinsufficiency of NSD1 causes Sotos syndrome. Nat Genet 30 365-366... 

PINKl haploinsufficiency may be sufficient to cause disease because PINKl is detected in some LBs in sporadic PD, as well as in samples carrying only one mutant PINKl allele, which are clinically and pathologically indistinguishable from sporadic cases (Gandhi et al., 2006). 

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