De novo duplication of Xq22.1→q24 with a disruption of the NXF gene cluster in a mentally retarded woman with short stature and premature ovarian failure.
OBJECTIVE
To present molecular cytogenetic characterization of a de novo duplication of Xq22.1→q24 in a mentally retarded woman with short stature and premature ovarian failure.


METHODS
A 19-year-old woman presented with psychomotor retardation, developmental delay, mental retardation, short stature, low body weight, general muscle hypotonia, distal muscle hypotrophy of the lower extremities, elongated digits, scanty pubic and axillary hair, hypoplastic external female genitalia, and secondary amenorrhea but no clinical features of Pelizaeus-Merzbacher disease. Conventional cytogenetic analysis revealed a karyotype of 46,X,dup(X)(q22.1q24). Fluorescence in situ hybridization determined a direct duplication with a linear tandem orientation. Array comparative genomic hybridization demonstrated partial trisomy Xq [arr cgh Xq22.1q24 (101,490,234-119,070,188 bp)×3] with a 17.6-Mb duplication.


RESULTS
The duplicated region contained NXF2B, NXF4, NXF3, PLP1, and PGRMC1 genes. There was a disruption of the NXF gene cluster of Xcen-NXF5-NXF2-NXF2B-NXF4-NXF3-Xqter.


CONCLUSIONS
A duplication of Xq22.1→q24 with a disruption of the NXF gene cluster in female patients can be associated with clinical manifestations of mental retardation in addition to short stature and premature ovarian failure.
Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan. cpc_mmh@yahoo.com
Chih-Ping
CP
Chen
Yi-Ning
YN
Su
Hung-Hung
HH
Lin
Schu-Rern
SR
Chern
Fuu-Jen
FJ
Tsai
Pei-Chen
PC
Wu
Chen-Chi
CC
Lee
Yu-Ting
YT
Chen
Wayseen
W
Wang
D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001827:Body Height / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D020440:Gene Duplication / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D018991:Myelin Proteolipid Protein / Q000235:genetics; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D055815:Young Adult
D051792:Basic Helix-Loop-Helix Proteins; D008565:Membrane Proteins; D018991:Myelin Proteolipid Protein; D029543:Nucleocytoplasmic Transport Proteins; D016601:RNA-Binding Proteins; D011980:Receptors, Progesterone; C481603:NPAS4 protein, human; C436949:NXF3 protein, human; C443839:NXF5 protein, human; C533515:Nxf2 protein, human; C115296:PGRMC1 protein, human; C472930:PLP1 protein, human