Hypoalphalipoproteinemia, Primary, 1

A number sign (#) is used with this entry because of evidence that primary hypoalphalipoproteinemia-1 is caused by heterozygous mutation in the ABC1 gene (ABCA1; 600046) on chromosome 9q31, which is also the site of mutations causing Tangier disease (205400).

Description

Twenty to 30% of early familial coronary heart disease (CHD) is ascribed to hypoalphalipoproteinemia, or high density lipoprotein deficiency. Although not initially recognized as a predisposing dyslipidemia, extensive epidemiologic work has implicated low high-density lipoprotein cholesterol (HDLC) levels in increased risk of cardiovascular disease, and low HDLC is considered to be a true dyslipidemic syndrome (Warnick and Wood, 1995).

Primary hypoalphalipoproteinemia-2 (618463) is caused by mtation in the APOA1 gene (107680) on chromosome 11q23.

Clinical Features

As in Tangier disease, an autosomal recessive disorder, the dominantly inherited disorder familial hypoalphalipoproteinemia shows a reduction in cellular cholesterol efflux (Marcil et al., 1999).

Mapping

After demonstrating mutations in the ABC1 gene in patients with Tangier disease, Brooks-Wilson et al. (1999) studied 4 French Canadian families with familial hypoalphalipoproteinemia. Linkage analysis revealed a maximum lod score of 9.67 at a recombination fraction of 0.0 at D9S277, the region to which Tangier disease had been mapped. These 2 diseases had hitherto been considered distinct, with different clinical and biochemical characteristics.

Molecular Genetics

In affected members of French Canadian families with hypoalphalipoproteinemia, Brooks-Wilson et al. (1999) identified heterozygous mutations in the ABC1 gene (600046.0001-600046.0004). One of the families had previously been studied by Marcil et al. (1995).