TY - JOUR
T1 - Characterization of an unbalanced translocation causing 3q28qter duplication and 10q26.2qter deletion in a patient with global developmental delay and self-injury
AU - Osei-Owusu, Ikeoluwa A.
AU - Norris, Alexis L.
AU - Joynt, Anya T.
AU - Thorpe, Jeremy
AU - Cho, Soonweng
AU - Tierney, Elaine
AU - Schmidt, Jonathan
AU - Hagopian, Louis
AU - Harris, Jacqueline
AU - Pevsner, Jonathan
N1 - Funding Information:
J.P. was supported by Intellectual and Developmental Disabilities Research Center (Grant U54 HD079123) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the support of an anonymous donor. I.A.O-O. was supported by R36 MH118005. DDG2P has been jointly funded through a MRC University Unit grant to the MRC Human Genetics Unit, the Transforming Genomic Medicine Initiative (TGMI) (Wellcome Strategic Award; grant number 200990/Z/16/Z), and the Deciphering Developmental Disorder study (Health Innovation Challenge Fund; grant number HICF-1009-003).
Publisher Copyright:
© 2020 Osei-Owusu et al.
PY - 2020/12
Y1 - 2020/12
N2 - Chromosomal structural variation can cause severe neurodevelopmental and neuropsychiatric phenotypes. Here we present a nonverbal female adolescent with severe stereotypic movement disorder with severe problem behavior (e.g., self-injurious behavior, aggression, and disruptive and destructive behaviors), autism spectrum disorder, severe intellectual disability, attention deficit hyperactivity disorder, and global developmental delay. Previous cytogenetic analysis revealed balanced translocations present in the patient’s apparently normal mother. We hypothesized the presence of unbalanced translocations in the patient due to maternal history of spontaneous abortions. Whole-genome sequencing and whole-genome optical mapping, complementary next-generation genomic technologies capable of the accurate and robust detection of structural variants, identified t(3;10), t(10;14), and t(3;14) three-way balanced translocations in the mother and der(10)t(3;14;10) and der(14)t(3;14;10) translocations in the patient. Instead of a t(3;10), she inherited a normal maternal copy of Chromosome 3, resulting in an unbalanced state of a 3q28qter duplication and 10q26.2qter deletion. Copy-imbalanced genes in one or both of these regions, such as DLG1, DOCK1, and EBF3, may contribute to the patient’s phenotype that spans neurodevelopmental, musculoskeletal, and psychiatric domains, with the possible contribution of a maternally inherited 15q13.2q13.3 deletion.
AB - Chromosomal structural variation can cause severe neurodevelopmental and neuropsychiatric phenotypes. Here we present a nonverbal female adolescent with severe stereotypic movement disorder with severe problem behavior (e.g., self-injurious behavior, aggression, and disruptive and destructive behaviors), autism spectrum disorder, severe intellectual disability, attention deficit hyperactivity disorder, and global developmental delay. Previous cytogenetic analysis revealed balanced translocations present in the patient’s apparently normal mother. We hypothesized the presence of unbalanced translocations in the patient due to maternal history of spontaneous abortions. Whole-genome sequencing and whole-genome optical mapping, complementary next-generation genomic technologies capable of the accurate and robust detection of structural variants, identified t(3;10), t(10;14), and t(3;14) three-way balanced translocations in the mother and der(10)t(3;14;10) and der(14)t(3;14;10) translocations in the patient. Instead of a t(3;10), she inherited a normal maternal copy of Chromosome 3, resulting in an unbalanced state of a 3q28qter duplication and 10q26.2qter deletion. Copy-imbalanced genes in one or both of these regions, such as DLG1, DOCK1, and EBF3, may contribute to the patient’s phenotype that spans neurodevelopmental, musculoskeletal, and psychiatric domains, with the possible contribution of a maternally inherited 15q13.2q13.3 deletion.
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U2 - 10.1101/MCS.A005884
DO - 10.1101/MCS.A005884
M3 - Article
C2 - 33335013
AN - SCOPUS:85098675803
SN - 2373-2873
VL - 6
JO - Cold Spring Harbor Molecular Case Studies
JF - Cold Spring Harbor Molecular Case Studies
IS - 6
M1 - a005884
ER -