TY - JOUR
T1 - Subtelomeric deletion of chromosome 10p15.3
T2 - Clinical findings and molecular cytogenetic characterization
AU - Descipio, Cheryl
AU - Conlin, Laura
AU - Rosenfeld, Jill
AU - Tepperberg, James
AU - Pasion, Romela
AU - Patel, Ankita
AU - McDonald, Marie T.
AU - Aradhya, Swaroop
AU - Ho, Darlene
AU - Goldstein, Jennifer
AU - McGuire, Marianne
AU - Mulchandani, Surabhi
AU - Medne, Livija
AU - Rupps, Rosemarie
AU - Serrano, Alvaro H.
AU - Thorland, Erik C.
AU - Tsai, Anne C.H.
AU - Hilhorst-Hofstee, Yvonne
AU - Ruivenkamp, Claudia A.L.
AU - Van Esch, Hilde
AU - Addor, Marie Claude
AU - Martinet, Danielle
AU - Mason, Thornton B.A.
AU - Clark, Dinah
AU - Spinner, Nancy B.
AU - Krantz, Ian D.
PY - 2012/9
Y1 - 2012/9
N2 - We describe 19 unrelated individuals with submicroscopic deletions involving 10p15.3 characterized by chromosomal microarray (CMA). Interestingly, to our knowledge, only two individuals with isolated, submicroscopic 10p15.3 deletion have been reported to date; however, only limited clinical information is available for these probands and the deleted region has not been molecularly mapped. Comprehensive clinical history was obtained for 12 of the 19 individuals described in this study. Common features among these 12 individuals include: cognitive/behavioral/developmental differences (11/11), speech delay/language disorder (10/10), motor delay (10/10), craniofacial dysmorphism (9/12), hypotonia (7/11), brain anomalies (4/6) and seizures (3/7). Parental studies were performed for nine of the 19 individuals; the 10p15.3 deletion was de novo in seven of the probands, not maternally inherited in one proband and inherited from an apparently affected mother in one proband. Molecular mapping of the 19 individuals reported in this study has identified two genes, ZMYND11 (OMIM 608668) and DIP2C (OMIM 611380; UCSC Genome Browser), mapping within 10p15.3 which are most commonly deleted. Although no single gene has been identified which is deleted in all 19 individuals studied, the deleted region in all but one individual includes ZMYND11 and the deleted region in all but one other individual includes DIP2C. There is not a clearly identifiable phenotypic difference between these two individuals and the size of the deleted region does not generally predict clinical features. Little is currently known about these genes complicating a direct genotype/phenotype correlation at this time. These data however, suggest that ZMYND11 and/or DIP2C haploinsufficiency contributes to the clinical features associated with 10p15 deletions in probands described in this study.
AB - We describe 19 unrelated individuals with submicroscopic deletions involving 10p15.3 characterized by chromosomal microarray (CMA). Interestingly, to our knowledge, only two individuals with isolated, submicroscopic 10p15.3 deletion have been reported to date; however, only limited clinical information is available for these probands and the deleted region has not been molecularly mapped. Comprehensive clinical history was obtained for 12 of the 19 individuals described in this study. Common features among these 12 individuals include: cognitive/behavioral/developmental differences (11/11), speech delay/language disorder (10/10), motor delay (10/10), craniofacial dysmorphism (9/12), hypotonia (7/11), brain anomalies (4/6) and seizures (3/7). Parental studies were performed for nine of the 19 individuals; the 10p15.3 deletion was de novo in seven of the probands, not maternally inherited in one proband and inherited from an apparently affected mother in one proband. Molecular mapping of the 19 individuals reported in this study has identified two genes, ZMYND11 (OMIM 608668) and DIP2C (OMIM 611380; UCSC Genome Browser), mapping within 10p15.3 which are most commonly deleted. Although no single gene has been identified which is deleted in all 19 individuals studied, the deleted region in all but one individual includes ZMYND11 and the deleted region in all but one other individual includes DIP2C. There is not a clearly identifiable phenotypic difference between these two individuals and the size of the deleted region does not generally predict clinical features. Little is currently known about these genes complicating a direct genotype/phenotype correlation at this time. These data however, suggest that ZMYND11 and/or DIP2C haploinsufficiency contributes to the clinical features associated with 10p15 deletions in probands described in this study.
KW - 10p15.3
KW - Chromosomal microarray (CMA)
KW - DIP2C
KW - Deletion
KW - ZMYND11
UR - http://www.scopus.com/inward/record.url?scp=84865551333&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865551333&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.35574
DO - 10.1002/ajmg.a.35574
M3 - Article
C2 - 22847950
AN - SCOPUS:84865551333
SN - 1552-4825
VL - 158 A
SP - 2152
EP - 2161
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 9
ER -