Novel mutations in ABCA1 gene in Japanese patients with Tangier disease and familial high density lipoprotein deficiency with coronary heart disease

Mutations in the ATP-binding cassette transporter I (ABCA1) gene have been recently identified as the molecular defect in Tangier disease (TD) and fam ilial high density lipoprotein deficiency (FHA). We here report novel mutat ions in the ABCA1 gene in two sisters from a Japanese family with TD who ha ve been described previously (S. Ohtaki, H. Nakagawa, N. Kida, H. Nakamura, K. Tsuda, S. Yokoyama, T. Yamamura, S. Tajima, A. Yamamoto, Atherosclerosi s 49 (1983)) and a family with FHA. Both probands of TD and FHA developed c oronary heart disease. Sequence analysis of the ABCA1 gene from the patient s with TD revealed a homozygous G to A transition at nucleotide 3805 of the cDNA resulting in the substitution of Asp 1229 with Asn in exon 27, and a C to T at nucleotide 6181 resulting in the substitution of Arg 2021 with Tr p in exon 47. Sequence analysis of the ABCA1 gene from the FHA patient reve aled a homozygous 4 bp CGCC deletion from nucleotide 3787 to 3790 resulting in premature termination by frameshift at codon 1224. These mutations were confirmed by restriction digestion analysis, and were not found in 141 con trol subjects. Our findings indicate that mutations in the ABCA1 gene are a ssociated with TD as well as FHA. (C) 2001 Elsevier Science B.V. All rights reserved.