Familial interstitial Xq27.3q28 duplication encompassing the FMR1 gene but not the MECP2 gene causes a new syndromic mental retardation condition.
X-linked mental retardation is a common disorder that accounts for 5-10% of cases of mental retardation in males. Fragile X syndrome is the most common form resulting from a loss of expression of the FMR1 gene. On the other hand, partial duplication of the long arm of the X chromosome is uncommon. It leads to functional disomy of the corresponding genes and has been reported in several cases of mental retardation in males. In this study, we report on the clinical and genetic characterization of a new X-linked mental retardation syndrome characterized by short stature, hypogonadism and facial dysmorphism, and show that this syndrome is caused by a small Xq27.3q28 interstitial duplication encompassing the FMR1 gene. This family broadens the phenotypic spectrum of FMR1 anomalies in an unexpected manner, and we suggest that this condition may represent the fragile X syndrome "contre-type".
Département de Génétique, Université Paris Descartes, INSERM U781, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France. marlene.rio@nck.aphp.fr
Marlène
M
Rio
Valérie
V
Malan
Sarah
S
Boissel
Annick
A
Toutain
Ghislaine
G
Royer
Stéphanie
S
Gobin
Nicole
N
Morichon-Delvallez
Catherine
C
Turleau
Jean-Paul
JP
Bonnefont
Arnold
A
Munnich
Michel
M
Vekemans
Laurence
L
Colleaux
D000328:Adult; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics*; D019066:Facies; D005191:Family Characteristics; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D020440:Gene Duplication; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D010375:Pedigree; D011247:Pregnancy; D013577:Syndrome
D051860:Fragile X Messenger Ribonucleoprotein 1; D051783:Methyl-CpG-Binding Protein 2; C497392:MECP2 protein, human