Galactosemia caused by a point mutation that activates cryptic donor splice site in the galactose-1-phosphate uridyltransferase gene

Journal Article · Sun Aug 01 04:00:00 EDT 1993 · Genomics; (United States)

DOI:https://doi.org/10.1006/geno.1993.1363· OSTI ID:7225713

Wadelius, C; Lagerkvist, A ^[1]; Molin, A K; Larsson, A ^[2]; Von Doebeln, U ^[3]

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1. Univ. Hospital, Uppsala (Sweden) Uppsala Univ. (Sweden)
2. Univ. Hospital, Uppsala (Sweden)
3. Karolinska Institute, Stockholm (Sweden)

Galactosemia affects 1/84,000 in Sweden and is manifested in infancy when the child is exposed to galactose in the diet. If untreated there is a risk of severe early symptoms and, even with a lactose-free diet, late symptoms such as mental retardation and ovarial dysfunction may develop. In classical galactosemia, galactose-1-phosphate uridyltransferase (GALT) (EC 2.7.7.12) is defective and the normal cDNA sequence of this enzyme has been characterized. Recently eight mutations leading to galactosemia were published. Heparinized venous blood was drawn from a patient with classical galactosemia. In the cDNA from the patient examined, an insertion of 54 bp was found at position 1087. Amplification of the relevant genomic region of the patient's DNA was performed. Exon-intron boundaries and intronic sequences thus determined revealed that the 54-bp insertion was located immediately downstream of exon 10. It was further found that the patient was heterozygous for a point mutation, changing a C to a T (in 5 of 9 clones) at the second base in the intron downstream of the insertion. This alteration creates a sequence which, as well as the ordinary splice site, differs in only two positions from the consensus sequence. It was found that the mutation occurred in only one of the 20 alleles from galactosemic patients and in none of the 200 alleles from normal controls. The mutation is inherited from the mother, who also was found to express the 54-bp-long insertion at the mRNA level. Sequences from the 5[prime] end of the coding region were determined after genomic amplification, revealing a sequence identical to that reported. The mutation on the paternal allele has not been identified. 9 refs., 1 fig.

• OSTI ID: 7225713
• Journal Information: Genomics; (United States), Journal Name: Genomics; (United States) Vol. 17:2; ISSN GNMCEP; ISSN 0888-7543
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
550900 -- Pathology
59 BASIC BIOLOGICAL SCIENCES
ALDEHYDES
CARBOHYDRATES
CLONING
DETECTION
DISEASES
DNA HYBRIDIZATION
DNA SEQUENCING
DNA-CLONING
ENZYMES
GALACTOSE
GENE AMPLIFICATION
GENE MUTATIONS
HEXOSES
HYBRIDIZATION
METABOLIC DISEASES
MONOSACCHARIDES
MUTATIONS
ORGANIC COMPOUNDS
POLYMERASE CHAIN REACTION
PROTEINS
SACCHARIDES
STRUCTURAL CHEMICAL ANALYSIS
TRANSFERASES