A child with intellectual disability and dysmorphism due to complex ring chromosome 6: identification of molecular mechanism with review of literature

被引:2
作者
Sheth, Frenny [1 ]
Liehr, Thomas [2 ]
Shah, Viraj [1 ]
Shah, Hillary [1 ]
Tewari, Stuti [1 ]
Solanki, Dhaval [3 ]
Trivedi, Sunil [1 ]
Sheth, Jayesh [1 ]
机构
[1] FRIGEs Inst Human Genet, FRIGE House,Jodhpur Gam Rd, Ahmadabad 380009, Gujarat, India
[2] Univ Clin Jena, Inst Human Genet, Klinikum 1, D-07747 Jena, Germany
[3] Mantra Child Neurol & Epilepsy Hosp, 3rd Floor,Oarnate Complex,Kalubha Rd, Kalanala 364001, Bhavanagar, India
关键词
Molecular karyotyping; Molecular cytogenetics; Haploinsufficiency; Ring chromosome; R(6); 6Q TERMINAL DELETION; PERIVENTRICULAR HETEROTOPIA; DEVELOPMENTAL ABNORMALITIES; FOXC1; GENE; DUPLICATIONS; ANOMALIES; REGION; EYE;
D O I
10.1186/s13052-018-0571-0
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Background: Ring chromosome 6 (r(6)) is a rare disorder that mainly occurs as a 'de novo' event. Nonetheless, a wide phenotypic spectrum has been reported in r(6) cases, depending on breakpoints, size of involved region, copy number alterations and mosaicism of cells with r(6) and/or monosomy 6 due to loss of r(6). Case presentation: An 11-year-old male was referred with developmental delay, intellectual disability and microcephaly. Physical examination revealed additionally short stature and multiple facial dysmorphisms. Banding cytogenetic studies revealed a karyotype of mos 46,XY,r(6)(p25.3q27)[54]/45,XY,-6[13]/46,XY,r(6)(::p25.3 -> q27::p25.3 -> q27::)[13]/46,XY[6]/47,XY,r(6)(p25.3q27)x2[2]dn. Additionally, molecular karyotyping and molecular cytogenetics confirmed the breakpoints and characterized a 1.3Mb contiguous duplication at 6p25.3. Conclusion: The present study has accurately identified copy number alterations caused by ring chromosome formation. A review of the literature suggests that hemizygous expression of TBP gene in 6q27 similar to qter, is likely to be the underlying cause of the phenotype. The phenotypic correlation and clinical severity in r(6) cases continue to remain widely diverse in spite of numerous reports of genomic variations.
引用
收藏
页数:9
相关论文
共 38 条
[1]  
Ahzad Hadi Ahmad, 2010, Kobe J Med Sci, V56, pE79
[2]  
Andrieux J, 2005, EUR J MED GENET, V199, P206
[3]   Dissecting the genetic complexity of human 6p deletion syndromes by using a region-specific, phenotype-driven mouse screen [J].
Bogani, D ;
Willoughby, C ;
Davies, J ;
Kaur, K ;
Mirza, G ;
Paudyal, A ;
Haines, H ;
McKeone, R ;
Cadman, M ;
Pieles, G ;
Schneider, JE ;
Bhattacharya, S ;
Hardy, A ;
Nolan, PM ;
Tripodis, N ;
Depew, MJ ;
Chandrasekara, R ;
Duncan, G ;
Sharpe, PT ;
Greenfield, A ;
Denny, P ;
Brown, SDM ;
Ragoussis, J ;
Arkell, RM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (35) :12477-12482
[4]   RING CHROMOSOME-6 IN A CHILD WITH MINIMAL ABNORMALITIES [J].
CARNEVALE, A ;
BLANCO, B ;
CASTILLO, J ;
DELCASTILLO, V ;
DOMINGUEZ, D .
AMERICAN JOURNAL OF MEDICAL GENETICS, 1979, 4 (03) :271-277
[5]   Array-CGH characterization and genotype-phenotype analysis in a patient with a ring chromosome 6 [J].
Ciocca, Laura ;
Surace, Cecilia ;
Digilio, Maria Cristina ;
Roberti, Maria Cristina ;
Sirleto, Pietro ;
Lombardo, Antonietta ;
Russo, Serena ;
Brizi, Valerio ;
Grotta, Simona ;
Cini, Claudio ;
Angioni, Adriano .
BMC MEDICAL GENOMICS, 2013, 6
[6]   Periventricular heterotopia in 6q terminal deletion syndrome: role of the C6orf70 gene [J].
Conti, Valerio ;
Carabalona, Aurelie ;
Pallesi-Pocachard, Emilie ;
Parrini, Elena ;
Leventer, Richard J. ;
Buhler, Emmanuelle ;
McGillivray, George ;
Michel, Francois J. ;
Striano, Pasquale ;
Mei, Davide ;
Watrin, Francoise ;
Lise, Stefano ;
Pagnamenta, Alistair T. ;
Taylor, Jenny C. ;
Kini, Usha ;
Clayton-Smith, Jill ;
Novara, Francesca ;
Zuffardi, Orsetta ;
Dobyns, William B. ;
Scheffer, Ingrid E. ;
Robertson, Stephen P. ;
Berkovic, Samuel F. ;
Represa, Alfonso ;
Keays, David A. ;
Cardoso, Carlos ;
Guerrini, Renzo .
BRAIN, 2013, 136 :3378-3394
[7]   Calibration of 6q subtelomere deletions to define genotype/pheno type correlations [J].
Eash, D ;
Waggoner, D ;
Chung, J ;
Stevenson, D ;
Martinc, CL .
CLINICAL GENETICS, 2005, 67 (05) :396-403
[8]  
FRIED K, 1975, CLIN GENET, V7, P192
[9]   Mechanisms of ring chromosome formation, ring instability and clinical consequences [J].
Guilherme, Roberta S. ;
Meloni, Vera F. Ayres ;
Kim, Chong A. ;
Pellegrino, Renata ;
Takeno, Sylvia S. ;
Spinner, Nancy B. ;
Conlin, Laura K. ;
Christofolini, Denise M. ;
Kulikowski, Leslie D. ;
Melaragno, Maria I. .
BMC MEDICAL GENETICS, 2011, 12
[10]   Molecular characterization of a de novo ring chromosome 6 in a growth retarded but otherwise healthy woman [J].
Hoeckner, Martina ;
Utermann, Barbara ;
Erdel, Martin ;
Fauth, Christine ;
Utermann, Gerd ;
Kotzot, Dieter .
AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2008, 146A (07) :925-929