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先天性乳糖酶缺乏症中乳糖酶-植物甜素水解酶的功能缺失变体是运输缺陷且无功能的。

Hypomorphic variants of lactase-phlorizin hydrolase in congenital lactase deficiency are trafficking incompetent and functionally inactive.

机构信息

Department of Biochemistry, University of Veterinary Medicine, Bünteweg 17, 30559 Hannover, Germany; Department of Pediatrics, University Medical Center Eppendorf, Martinistr. 52, 20251 Hamburg, Germany.

Department of Biochemistry, University of Veterinary Medicine, Bünteweg 17, 30559 Hannover, Germany.

出版信息

Biochim Biophys Acta Mol Basis Dis. 2022 Apr 1;1868(4):166338. doi: 10.1016/j.bbadis.2022.166338. Epub 2022 Jan 8.

DOI:10.1016/j.bbadis.2022.166338

PMID:35007711

Abstract

Patients with the rare autosomal recessive disorder congenital lactase deficiency (CLD) present with severe, potentially life-threatening symptoms shortly after birth. Several variants have been characterized within the gene for lactase-phlorizin hydrolase (LCT) that are associated with CLD. Here, we analyze at the biochemical and cellular levels LCT mutants harboring the genetic variants p.Y1390*, p.E1612*, p.S1150Pfs*19, p.S1121L, p.R1587H, and p.S688P. Our data unequivocally demonstrate that these mutants are absolutely transport incompetent, some of which are readily degraded, and are enzymatically inactive. The current study contributes to and expands our understanding on the pathogenesis of CLD at the molecular level.

摘要

患有罕见常染色体隐性遗传疾病先天性乳糖酶缺乏症（CLD）的患者在出生后不久就会出现严重的、可能危及生命的症状。在乳糖酶-根皮苷水解酶（LCT）基因中已经鉴定出与 CLD 相关的几种变体。在这里，我们在生化和细胞水平上分析了携带遗传变异 p.Y1390*、p.E1612*、p.S1150Pfs*19、p.S1121L、p.R1587H 和 p.S688P 的 LCT 突变体。我们的数据明确表明，这些突变体完全没有转运能力，其中一些很容易被降解，并且没有酶活性。本研究有助于并扩展了我们对 CLD 发病机制的分子水平的理解。