New human sodium/glucose cotransporter gene (KST1): identification, characterization, and mutation analysis in ICCA (infantile convulsions and choreoathetosis) and BFIC (benign familial infantile convulsions) families

Gene. 2002 Feb 20;285(1-2):141-8. doi: 10.1016/s0378-1119(02)00416-x.

Abstract

Cotransporters represent a major class of proteins that make use of ion gradients to drive active transport of substrate into cells. A new human gene, KST1, encoding a member of the sodium/glucose cotransporter family, was identified onto human chromosome 16p12-p11. This genomic region contains a major gene responsible for a syndrome of infantile convulsions and paroxysmal dyskinesia (ICCA syndrome), inherited as an autosomal dominant trait, as well as for benign familial infantile convulsions (BFIC). The entire coding sequence of the human KST1 gene was determined using a combination of methods including in silico comparison of its rabbit orthologous DNA complementary to RNA (cDNA) to the corresponding human genomic sequences, reverse transcription-polymerase chain reaction on human brain RNA, 5' and 3' rapid amplification of cDNA ends. The gene is divided into 16 exons and the predicted protein of 675 amino acids contains 14 transmembrane domains. It shares significant homology to the sodium-glucose transporter 1 cotransporter proteins. An alternatively spliced transcript resulting from the skipping of exon 6 led to a predicted protein lacking the 4th transmembrane domain. As ion transporters are good candidates for a large variety of human diseases, including paroxysmal disorders, a mutation search was performed in four families with ICCA or BFIC syndromes. No pathogenic mutation was found, although several polymorphic variants with amino acids exchanges were identified. Due to its broad expression in human tissues, the human KST1 gene could be involved in several other diseases mapped to human chromosome 16p12-p11.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Athetosis / complications
  • Athetosis / genetics
  • Base Sequence
  • Blotting, Northern
  • Chorea / complications
  • Chorea / genetics
  • Cloning, Molecular
  • DNA Mutational Analysis
  • DNA, Complementary / chemistry
  • DNA, Complementary / genetics
  • Epilepsy, Benign Neonatal / genetics
  • Exons
  • Family Health
  • Gene Expression
  • Genes / genetics
  • Humans
  • Infant
  • Infant, Newborn
  • Introns
  • Molecular Sequence Data
  • Monosaccharide Transport Proteins / genetics*
  • Mutation
  • Phylogeny
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Seizures / complications
  • Seizures / genetics
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Sodium-Glucose Transport Proteins
  • Symporters*

Substances

  • DNA, Complementary
  • Monosaccharide Transport Proteins
  • RNA, Messenger
  • SLC5A11 protein, human
  • Sodium-Glucose Transport Proteins
  • Symporters

Associated data

  • GENBANK/AY044906