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Case Reports
. 2009 Jan 22:9:8.
doi: 10.1186/1471-230X-9-8.

Four novel mutations in the lactase gene (LCT) underlying congenital lactase deficiency (CLD)

Suvi Torniainen  1 , Roberta Freddara, Taina Routi, Carolien Gijsbers, Carlo Catassi, Pia Höglund, Erkki Savilahti, Irma Järvelä
Affiliations
Case Reports

Four novel mutations in the lactase gene (LCT) underlying congenital lactase deficiency (CLD)

Suvi Torniainen et al. BMC Gastroenterol. .

Abstract

Background: Congenital lactase deficiency (CLD) is a severe gastrointestinal disorder of newborns. The diagnosis is challenging and based on clinical symptoms and low lactase activity in intestinal biopsy specimens. The disease is enriched in Finland but is also present in other parts of the world. Mutations encoding the lactase (LCT) gene have recently been shown to underlie CLD. The purpose of this study was to identify new mutations underlying CLD in patients with different ethnic origins, and to increase awareness of this disease so that the patients could be sought out and treated correctly.

Methods: Disaccharidase activities in intestinal biopsy specimens were assayed and the coding region of LCT was sequenced from five patients from Europe with clinical features compatible with CLD. In the analysis and prediction of mutations the following programs: ClustalW, Blosum62, PolyPhen, SIFT and Panther PSEC were used.

Results: Four novel mutations in the LCT gene were identified. A single nucleotide substitution leading to an amino acid change S688P in exon 7 and E1612X in exon 12 were present in a patient of Italian origin. Five base deletion V565fsX567 leading to a stop codon in exon 6 was found in one and a substitution R1587H in exon 12 from another Finnish patient. Both Finnish patients were heterozygous for the Finnish founder mutation Y1390X. The previously reported mutation G1363S was found in a homozygous state in two siblings of Turkish origin.

Conclusion: This is the first report of CLD mutations in patients living outside Finland. It seems that disease is more common than previously thought. All mutations in the LCT gene lead to a similar phenotype despite the location and/or type of mutation.

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Figures

Figure 1
Figure 1
Conservation of mutations sites. ClustalW alignment of human LPH protein and LPH proteins from other species showing the conservation of the region for mutations V565fsX567 (A), S688P (B), R1587H (C) and E1612X (C).
Figure 2
Figure 2
Schematic presentation of the LCT gene and locations of the mutations. Cleavage sites are R734/L735 and R867/A868.
See this image and copyright information in PMC

References

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