TM4SF10 gene sequencing in XLMR patients identifies common polymorphisms but no disease-associated mutation.
BACKGROUND
The TM4SF10 gene encodes a putative four-transmembrane domains protein of unknown function termed Brain Cell Membrane Protein 1 (BCMP1), and is abundantly expressed in the brain. This gene is located on the short arm of human chromosome X at p21.1. The hypothesis that mutations in the TM4SF10 gene are associated with impaired brain function was investigated by sequencing the gene in individuals with hereditary X-linked mental retardation (XLMR).


METHODS
The coding region (543 bp) of TM4SF10, including intronic junctions, and the long 3' untranslated region (3 233 bp), that has been conserved during evolution, were sequenced in 16 male XLMR patients from 14 unrelated families with definite, or suggestive, linkage to the TM4SF10 gene locus, and in 5 normal males.


RESULTS
Five sequence changes were identified but none was found to be associated with the disease. Two of these changes correspond to previously known SNPs, while three other were novel SNPs in the TM4SF10 gene.


CONCLUSIONS
We have investigated the majority of the known MRX families linked to the TM4SF10 gene region. In the absence of mutations detected, our study indicates that alterations of TM4SF10 are not a frequent cause of XLMR.
Christophe-Hobertus
Christiane
C
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles, IBMM, B-6041 Gosselies, Belgium. chobertu@ulb.ac.be
Kooy
Frank
F
Gecz
Jozef
J
Abramowicz
Marc J
MJ
Holinski-Feder
Elke
E
Schwartz
Charles
C
Christophe
Daniel
D
D020413:3' Untranslated Regions / Q000737:chemistry; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
D020413:3' Untranslated Regions; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C491469:TMEM47 protein, human