Isolated 9p Duplication With der(Y)t(Y;9)(q12;p13.2) in a Male Patient With Cardiac Defect and Mental Retardation Confirmed by Chromosomal Microarray

Dear Editor, 9p duplication syndrome is characterized by craniofacial dysmorphism, digital abnormalities, short stature, short neck, developmental delay, and mental retardation [1]. It can also accompany rare phenotypes including cardiac defect [2, 3], psychotic behavior [4], autism spectrum disorder (ASD) [5], and hearing loss [6]. Phenotypes of 9p duplication correlate with the size and position of the involved region [6]. Most 9p duplications originate from parental balanced translocation, usually between chromosome 9 and other autosomes [1, 4]. Therefore, accompanying partial monosomy of chromosome 9 or abnormalities of other chromosomes may complicate the understanding on the genotype-phenotype correlation of 9p duplication [1]. Reports on isolated 9p duplication, excluding cases with partial monosomy of chromosome 9 or other chromosomes, are relatively uncommon [1]. Here, we report an isolated 9p duplication case confirmed by chromosomal microarray (CMA) analysis. The patient was a 38-yr-old Korean man with severe mental retardation and no other underlying disease previously diagnosed. On the day of admission, he had a sudden cardiac arrest due to ventricular fibrillation at his work facility. Further evaluation after resuscitation and admission revealed severe aortic stenosis from bicuspid aortic valve. Tracheomalacia was noted by fiber-optic bronchoscopy (FOB). Brain computed tomography found decreased brain volume and mild hydrocephalus. On the basis of his dysmorphic features (coarse face and short neck) and cardiac anomaly, the attending clinician suspected DiGeorge syndrome, but FISH targeting the TUPLE1 gene (Abbott Molecular, Downers Grove, IL, USA) showed negative results. In G-banded karyotyping, material of unknown origin was inserted into the heterochromatin portion of the Y chromosome (Fig. 1A). CMA analysis with a CytoScan 750K array (Affymetrix, Santa Clara, CA, USA) revealed a 38.5 mega base (Mb) duplication on 9p24.3p13.2 (Fig. 1B). The final cytogenetic result for the patient was reported as 46,X,der(Y)t(Y;9)(q12;p13.2).arr[hg19] 9p24.3p13.2(208,454-38,689,749)x3 according to the International System for Human Cytogenetic Nomenclature 2013. The duplicated region in our patient includes a critical region of 9p duplication syndrome (9p22.3 to 9p22.2) [5] and contains 255 genes and 147 Online Mendelian Inheritance in Man