Identification of patients with abetalipoproteinemia and homozygous familial hypobetalipoproteinemia in Tunisia.
BACKGROUND
Abetalipoproteinemia (ABL) and Homozygous Familial Hypobetalipoproteinemia (Ho-FHBL) are rare monogenic diseases characterised by very low plasma levels of cholesterol and triglyceride and the absence or a great reduction of apolipoprotein B (apoB)-containing lipoproteins. ABL results from mutations in the MTP gene; Ho-FHBL may be due to mutations in the APOB gene.


METHODS
We sequenced MTP and APOB genes in three Tunisian children, born from consanguineous marriage, with very low levels of plasma apoB-containing lipoproteins associated with severe intestinal fat malabsorption.


RESULTS
Two of them were found to be homozygous for two novel mutations in intron 5 (c.619-3T>G) and in exon 8 (c.923 G>A) of the MTP gene, respectively. The c.619-3T>G substitution caused the formation of an abnormal mRNA devoid of exon 6, predicted to encode a truncated MTP of 233 amino acids. The c.923 G>A is a nonsense mutation resulting in a truncated MTP protein (p.W308X). The third patient was homozygous for a novel nucleotide deletion (c.2172delT) in exon 15 of APOB gene resulting in the formation of a truncated apoB of 706 amino acids (apoB-15.56).


CONCLUSIONS
These mutations are expected to abolish the apoB lipidation and the assembly of apoB-containing lipoproteins in both liver and intestine.
Najah
Mohamed
M
Research Unit of Genetic and Biologic Factors of Atherosclerosis, Faculty of Medicine, Monastir, Tunisia.
Di Leo
Enza
E
Awatef
Jelassi
J
Magnolo
Lucia
L
Imene
Jgurim
J
Pinotti
Elisa
E
Bahri
Mahjoub
M
Barsaoui
Sihem
S
Brini
Ines
I
Fekih
Moncef
M
Slimane
Mohamed Naceur
MN
Tarugi
Patrizia
P
D000012:Abetalipoproteinemia / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D052476:Hypobetalipoproteinemia, Familial, Apolipoprotein B / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D007223:Infant; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D014416:Tunisia; D055815:Young Adult
D001055:Apolipoproteins B; D002352:Carrier Proteins; C106092:microsomal triglyceride transfer protein