A clinical and genetic analysis of a child with supernumerary marker chromosome 15-caused mental retardation, intractable epilepsy, and central precocious puberty
GAO Zhi-Jie1, JIANG Qian2, CHEN Qian1, WANG Jing-Min3, PAN Hong4
Department of Neurology, Affiliated Children's Hospital of Capital Institute of Pediatrics, Beijing 100020, China
Abstract Supernumerary marker chromosome 15 is a rare chromosome abnormality. This paper reports the clinical diagnosis and treatment, as well as genetic defects, of a child with supernumerary marker chromosome 15. The patient was a 9.5-year-old girl who had mental and motor retardation since infancy, breast development at the age of 7 years, and seizures at the age of 8.5 years. Seizures occurred with various features and could not be controlled by a variety of antiepileptic drugs. No abnormalities were found by brain magnetic resonance imaging. Electroencephalogram showed frequent epileptiform discharges. G-banding karyotype analysis, fluorescence in situ hybridization, methylation-specific multiplex ligation-dependent probe amplification, and array comparative genomic hybridization identified a de novo 15q duplication in the patient. The maternal copy number increased in the 15q11-13 region. The form of genome rearrangement was 47,XX,+inv dup(15)(pter to q13:q13 to pter). The increased copy number in the 15q11-13 region is closely related to mental retardation, intractable epilepsy, and central precocious puberty. High-resolution karyotype analysis is recommended for children with unexplained mental retardation and epilepsy.
GAO Zhi-Jie,JIANG Qian,CHEN Qian et al. A clinical and genetic analysis of a child with supernumerary marker chromosome 15-caused mental retardation, intractable epilepsy, and central precocious puberty[J]. CJCP, 2018, 20(8): 652-657.
GAO Zhi-Jie,JIANG Qian,CHEN Qian et al. A clinical and genetic analysis of a child with supernumerary marker chromosome 15-caused mental retardation, intractable epilepsy, and central precocious puberty[J]. CJCP, 2018, 20(8): 652-657.
Liehr T, Karamysheva T, Merkas M, et al. Somatic Mosaicism in cases with small supernumerary marker chromosomes[J]. Curr Genomics, 2010, 11(6):432-439.
[2]
Park DH, Lim S, Park ES, et al. A nine-month-old boy with isodicentric chromosome 15:A case report[J]. Ann Rehabil Med, 2013, 37(2):291-294.
[3]
Battaglia A, Parrini B, Tancredi R. The behavioral phenotype of the idic(15) syndrome[J]. Am J Med Genet C Semin Med Genet, 2010, 154C(4):448-455.
[4]
Schinzel A, Niedrist D. Chromosome imbalances associated with epilepsy[J]. Am J Med Genet, 2001, 106(2):119-124.
Liehr T, Weise A. Frequency of small supernumerary marker chromosomes in prenatal, newborn, developmentally retarded and infertility diagnostics[J]. Int J Mol Med, 2007, 19(5):719-731.
[8]
Jafarighahfarokhi H, Moradichaleshtori M, Liehr T, et al. Small supernumerary marker chromosomes and their correlation with specific syndromes[J]. 2015, 4(1):140.
[9]
Balkan M, Isi H, Gedik A, et al. A small supernumerary marker chromosome, derived from chromosome 22, possibly associated with repeated spontaneous abortions[J]. Genet Mol Res, 2010, 9(3):1683-1689.
[10]
Manvelyan M, Riegel MM, Santos M, et al. Thirty-two new cases with small supernumerary marker chromosomes detected in connection with fertility problems:detailed molecular cytogenetic characterization and review of the literature[J]. Int J Mol Med, 2008, 21(6):705-714.
[11]
Magri C, Sacchetti E, Traversa M, et al. New copy number variations in schizophrenia[J]. PLoS One, 2010, 5(10):e13422.
[12]
Wang NJ, Liu D, Parokonny AS, et al. High-resolution molecular characterization of 15q11-q13 rearrangements by array comparative genomic hybridization (Array CGH) with detection of gene dosage[J]. Am J Hum Genet, 2004, 75(2):267-281.
[13]
Mignon-Ravix C, Depetris D, Luciani JJ, et al. Recurrent rearrangements in the proximal 15q11-q14 region:a new breakpoint cluster specific to unbalanced translocations[J]. Eur J Hum Genet, 2007, 15(4):432-440.
[14]
Locke DP, Segraves R, Nicholls RD, et al. BAC microarray analysis of 15q11-q13 rearrangements and the impact of segmental duplications[J]. J Med Genet, 2004, 41(3):175-182.
[15]
Wang NJ, Parokonny AS, Thatcher KN, et al. Multiple forms of atypical rearrangements generating supernumerary derivative chromosome 15[J]. BMC Genet, 2008, 9:2.
[16]
Al Ageeli E, Drunat S, Delanoë C, et al. Duplication of the 15q11-q13 region:clinical and genetic study of 30 new cases[J]. Eur J Med Genet, 2014, 57(1):5-14.
[17]
Verrotti A, Sertorio F, Matricardi S, et al. Electroclinical features of epilepsy in patients with InvDup(15)[J]. Seizure, 2017, 47:87-91.
[18]
Khokhar A, Agarwal S, Perez-Colon S. Williams syndrome and 15q duplication:Coincidence versus association[J]. Mol Syndromol, 2017, 8(1):50-54.
Settas N, Dacou-Voutetakis C, Karantza M, et al. Central precocious puberty in a girl and early puberty in her brother caused by a novel mutation in the MKRN3 gene[J]. J Clin Endocrinol Metab, 2014, 99(4):647-651.
[21]
Shin YL. An update on the genetic causes of central precocious puberty[J]. Ann Pediatr Endocrinol Metab, 2016, 21(2):66-69.
