Haploinsufficiency

Haploinsufficiency may arise from a de novo or inherited loss-of-function mutation in the variant allele, such that it yields little or no gene product (often a protein).

It is a rare inherited disorder characterized by abnormal skin manifestations, which results in bone marrow failure, pulmonary fibrosis and an increased predisposition to cancer.

A null mutation in motif D of the reverse transcriptase domain of the telomerase protein, hTERT, leads to this phenotype.

The hemizygosity of the elastin is responsible for supravalvular aortic stenosis, the obstruction in the left ventricular outflow of blood in the heart.

[5][6] Other examples include: The most direct method to detect haploinsufficiency is the heterozygous deletion of one allele in a model organism.

Haploinsufficiency model of dominant genetic disorders. A + is a normal allele. A − is a mutant allele with little or no function. In haplosufficiency (most genes), a single normal allele provides enough function, so A + A − individuals are healthy. In haploinsufficiency, a single normal allele does not provide enough function, so A + A − individuals have a genetic disorder.