A study of two Chinese patients with tetrasomy and pentasomy 15q11q13 including Prader-Willi/Angelman syndrome critical region present with developmental delays and mental impairment

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• 作者：Jing Yang (1)
  Yongchen Yang (2)
  Yi Huang (1)
  Yan Hu (3)
  Xi Chen (1)
  Hengjuan Sun (1)
  Zhibao Lv (2)
  Qian Cheng (3)
  Liming Bao (1) (2) (4)
  
• 关键词：Chromosome 15 ; Cytogenomic array ; Copy number ; Pentasomy ; Tetrasomy
• 刊名：BMC Medical Genetics
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：14
• 期：1
• 全文大小：898KB
• 参考文献：1. Knoll JH, Nicholls RD, Magenis RE, Graham JM Jr, Lalande M, Latt SA: Angelman and Prader-Willi syndromes share a common chromosome 15 deletion but differ in parental origin of the deletion. / Am J Med Genet 1989,32(2):285鈥?90. CrossRef
  2. Battaglia A: The inv dup(15) or idic(15) syndrome: a clinically recognisable neurogenetic disorder. / Brain Dev 2005,27(5):365鈥?69. CrossRef
  3. Ungaro P, Christian SL, Fantes JA, Mutirangura A, Black S, Reynolds J, Malcolm S, Dobyns WB, Ledbetter DH: Molecular characterisation of four cases of intrachromosomal triplication of chromosome 15q11-q14. / J Med Genet 2001,38(1):26鈥?4. CrossRef
  4. Kraoua L, Chaabouni M, Ewers E, Chelly I, Ouertani I, Ben Jemaa L, Maazoul F, Liehr T, Chaabouni H: Hexasomy of the Prader-Willi/Angelman critical region, including the OCA2 gene, in a patient with pigmentary dysplasia: case report. / Eur J Med Genet 2011,54(4):e446鈥?50. CrossRef
  5. Crolla JA, Harvey JF, Sitch FL, Dennis NR: Supernumerary marker 15 chromosomes: a clinical, molecular and FISH approach to diagnosis and prognosis. / Hum Genet 1995,95(2):161鈥?70. CrossRef
  6. Friedrich U, Nielsen J: Bisatellited extra small metacentric chromosome in newborns. / Clin Genet 1974,6(1):23鈥?1. CrossRef
  7. Webb T: Inv dup(15) supernumerary marker chromosomes. / J Med Genet 1994,31(8):585鈥?94. CrossRef
  8. Mann SM, Wang NJ, Liu DH, Wang L, Schultz RA, Dorrani N, Sigman M, Schanen NC: Supernumerary tricentric derivative chromosome 15 in two boys with intractable epilepsy: another mechanism for partial hexasomy. / Hum Genet 2004,115(2):104鈥?11. CrossRef
  9. Russell DJ, Avery LM, Rosenbaum PL, Raina PS, Walter SD, Palisano RJ: Improved scaling of the gross motor function measure for children with cerebral palsy: evidence of reliability and validity. / Phys Ther 2000,80(9):873鈥?85.
  10. Gesell A: The clinical supervision of child development. / Wis Med J 1949,48(2):119鈥?23.
  11. Wechsler D: / Wechesler Interlligence Scale for Children-Fourth Edition. San Antonin, TX: The Psychological Corporation; 2003.
  12. Arribas-Gil A, Matias C: A context dependent pair hidden Markov model for statistical alignment. / Stat Appl Genet Mol Biol 2012.,11(1): Article 5
  13. Dennis NR, Veltman MW, Thompson R, Craig E, Bolton PF, Thomas NS: Clinical findings in 33 subjects with large supernumerary marker(15) chromosomes and 3 subjects with triplication of 15q11-q13. / Am J Med Genet A 2006,140(5):434鈥?41.
  14. Kitsiou-Tzeli S, Tzetis M, Sofocleous C, Vrettou C, Xaidara A, Giannikou K, Pampanos A, Mavrou A, Kanavakis E: De novo interstitial duplication of the 15q11.2-q14 PWS/AS region of maternal origin: Clinical description, array CGH analysis, and review of the literature. / Am J Med Genet A 2010,152A(8):1925鈥?932. CrossRef
  15. Li H, Ji CY, Zong XN, Zhang YQ: Height and weight standardized growth charts for Chinese children and adolescents aged 0 to 18 years. / Chin J Pediatr 2009,47(7):487鈥?92.
  16. Li H: Growth standardized values and curves based on weight, length/height and head circumference for Chinese children under 7 years of age. / Chin J Pediatr 2009,47(3):173鈥?78.
  17. Kim SA, Kim JH, Park M, Cho IH, Yoo HJ: Association of GABRB3 polymorphisms with autism spectrum disorders in Korean trios. / Neuropsychobiology 2006,54(3):160鈥?65. CrossRef
  18. Sutcliffe JS, Han MK, Amin T, Kesterson RA, Nurmi EL: Partial duplication of the APBA2 gene in chromosome 15q13 corresponds to duplicon structures. / BMC Genomics 2003,4(1):15. CrossRef
  19. Olincy A, Harris JG, Johnson LL, Pender V, Kongs S, Allensworth D, Ellis J, Zerbe GO, Leonard S, Stevens KE: Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia. / Arch Gen Psychiatry 2006,63(6):630鈥?38. CrossRef
  20. Pujana MA, Nadal M, Guitart M, Armengol L, Gratacos M, Estivill X: Human chromosome 15q11-q14 regions of rearrangements contain clusters of LCR15 duplicons. / Eur J Hum Genet 2002,10(1):26鈥?5. CrossRef
  21. Mignon-Ravix C, Depetris D, Luciani JJ, Cuoco C, Krajewska-Walasek M, Missirian C, Collignon P, Delobel B, Croquette MF, Moncla A: Recurrent rearrangements in the proximal 15q11-q14 region: a new breakpoint cluster specific to unbalanced translocations. / Eur J Hum Genet 2007,15(4):432鈥?40. CrossRef
  22. Knoll JH, Nicholls RD, Magenis RE, Glatt K, Graham JM Jr, Kaplan L, Lalande M: Angelman syndrome: three molecular classes identified with chromosome 15q11q13-specific DNA markers. / Am J Hum Genet 1990,47(1):149鈥?54.
  23. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/14/9/prepub
  
• 作者单位：Jing Yang (1)
  Yongchen Yang (2)
  Yi Huang (1)
  Yan Hu (3)
  Xi Chen (1)
  Hengjuan Sun (1)
  Zhibao Lv (2)
  Qian Cheng (3)
  Liming Bao (1) (2) (4)
  
  1. Center for Clinical Molecular Medicine; Ministry of Education Key Laboratory of Child Development and Disorders; Key Laboratory of Pediatrics in Chongqing; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children鈥檚 Hospital of Chongqing Medical University, Chongqing, China
  2. Shanghai Children鈥檚 Hospital, Shanghai Children鈥檚 Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
  3. Department of Child Health Care and Growth Developmental and Psychological Health Center, Children鈥檚 Hospital of Chongqing Medical University, Chongqing, China
  4. Division of Human Genetics, Department of Pediatrics, Cincinnati Children鈥檚 Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, USA
  
• ISSN：1471-2350

文摘

Background The proximal chromosome 15q is prone to unequal crossover, leading to rearrangements. Although 15q11q13 duplications are common in patients with developmental delays and mental impairment, 15q aneusomies resulting in greater or equal to 4 copies of 15q11q13 are rare and no pentasomy 15q11q13 has been reported in the literature. Thus far, all reported high copy number 15q11q13 cases are from the West populations and no such study in Chinese patients have been documented. Dosage-response pattern of high copy number 15q11q13 on clinical presentations is still a subject for further study. Case Presentation In this study, we characterized two Han Chinese patients with high copy number 15q11q13. Using chromosome banding, high resolution SNP-based cytogenomic array, Fluorescence in situ hybridization, and PCR-based microsatellite analysis, we identified two patients with tetrasomy 15q11q13 and pentasomy 15q11q13. Both 15q11q13 aneusomies resulted from a maternally inherited supernumerary marker chromosome 15, and each was composed of two different sized 15q11q13 segments covering the Prader-Willi/Angelman critical region: one being about 10 Mb with breakpoints at BP1 and BP5 regions on 15q11 and 15q13, respectively, and another about 8 Mb in size with breakpoints at BP1 and BP4 regions on 15q. Both patients presented with similar clinical features that included neurodevelopmental delays, mental impairment, speech and autistic behavior, and mild dysmorphism. The patient with pentasomy 15q11q13 was more severely affected than the patient with tetrasomy 15q11q13. Low birth weight was noted in patient with pentasomy 15q1q13. Conclusions To the best of our knowledge, this is the first case of pentasomy 15q11q13 and the first study of high copy number 15q11q13 in Han Chinese patients. Our findings demonstrate that patients with tetrasomy and pentasomy of chromosome 15q11q13 share similar spectrum of phenotypes reported in other high copy number 15q11q13 patients in the West, and positive correlation between 15q11q13 copy number and degree of severity of clinical phenotypes. Low birth weight observed in the pentasomy 15q11q13 patient was not reported in other patients with high copy number 15q11q13. Additional studies would be necessary to further characterize high copy number 15q11q13 aneusomies.