Association of syndromic mental retardation with an Xq12q13.1 duplication encompassing the oligophrenin 1 gene.
OPHN1 mutations cause a syndromic form of mental retardation (MR) characterized by cerebellar hypoplasia, early hypotonia, motor and speech delay, with occasional seizures and strabismus. Here we report on a familial chromosome duplication spanning about 800 Kb of Xq12q13.1, associated with MR and a distinctive phenotype in the affected male, but not in his heterozygous mother. The parents were healthy and non-consanguineous with a history of three pregnancies. The first resulted in the birth of a boy with MR, motor impairment and seizures. The second pregnancy was terminated because of trisomy 18. At the time of the third, the first affected boy was analyzed by array-CGH, which revealed a 800 Kb duplication at Xq12q13.1, encompassing three genes, including OPHN1. This mutation was inherited from his healthy mother and was not present in any of the three maternal brothers. To our knowledge this is the first report of a clinical phenotype associated with duplication of Xq12q13.
Clinical Genetics Unit, Fondazione IRCCS, Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy. m.bedeschi@policlinico.mi.it
Maria Francesca
MF
Bedeschi
Antonio
A
Novelli
Laura
L
Bernardini
Cecilia
C
Parazzini
Vera
V
Bianchi
Barbara
B
Torres
Federica
F
Natacci
Maria Grazia
MG
Giuffrida
Paola
P
Ficarazzi
Bruno
B
Dallapiccola
Faustina
F
Lalatta
D000328:Adult; D000782:Aneuploidy; D001483:Base Sequence; D001921:Brain / Q000473:pathology; D041321:Chromosomes, Human, X / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000235:genetics / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008279:Magnetic Resonance Imaging; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D011247:Pregnancy; D013577:Syndrome; D049951:X Chromosome Inactivation
D003598:Cytoskeletal Proteins; D017931:DNA Primers; D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; C111952:OPHN1 protein, human