Loss of SLC38A5 and FTSJ1 at Xp11.23 in three brothers with non-syndromic mental retardation due to a microdeletion in an unstable genomic region.
Using high resolution X chromosome array-CGH we identified an interstitial microdeletion at Xp11.23 in three brothers with moderate to severe mental retardation (MR) without dysmorphic features. The extent of the deletion was subsequently delineated to about 50 kb by regular PCR and included only the SLC38A5 and FTSJ1 genes. The loss of the FTSJ1 MR gene in males is expected to result in the observed phenotype but the contribution of the deletion of the solute carrier SLC38A5 gene is less clear. Their mother also carries the deletion and completely inactivates the aberrant X chromosome. Interestingly, the distal breakpoint is situated within a 200 kb SSX repeat region that appears to stimulate recombination since subtle copy number changes often occur at this location and it is frequently involved in translocations in tumours. Since this apparent SSX unstable structure is flanked proximally by FTSJ1 and PQBP1, subtle deletions or duplications at this location would be expected to cause MR, as in our family. So far, we have screened a cohort of 300 patients but did not find additional aberrations at the FTSJ1 locus indicating that the frequency is likely to be low.
Froyen
Guy
G
Human Genome Laboratory, Department for Molecular and Developmental Genetics, VIB, Leuven, Belgium. guy.froyen@med.kuleuven.be
Bauters
Marijke
M
Boyle
Jackie
J
Van Esch
Hilde
H
Govaerts
Karen
K
van Bokhoven
Hans
H
Ropers
Hans-Hilger
HH
Moraine
Claude
C
Chelly
Jamel
J
Fryns
Jean-Pierre
JP
Marynen
Peter
P
Gecz
Jozef
J
Turner
Gillian
G
D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics*; D002872:Chromosome Deletion; D041321:Chromosomes, Human, X; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012729:Sex Chromosome Aberrations; D035781:Siblings; D049951:X Chromosome Inactivation
D026921:Amino Acid Transport Systems, Neutral; D009687:Nuclear Proteins; C424137:SLC38A5 protein, human; C490101:FTSJ1 protein, human; D008780:Methyltransferases