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

ObjectiveTo 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.Materials and MethodsA 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.ResultsThe 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.ConclusionA 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.