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Characterization of an unbalanced translocation causing 3q28qter duplication and 10q26.2qter deletion in a patient with global developmental delay and self-injury.

ABSTRACT: 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.

SUBMITTER: Osei-Owusu IA

PROVIDER: S-EPMC7784495 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Characterization of an unbalanced translocation causing 3q28qter duplication and 10q26.2qter deletion in a patient with global developmental delay and self-injury.

Osei-Owusu Ikeoluwa A IA Norris Alexis L AL Joynt Anya T AT Thorpe Jeremy J Cho Soonweng S Tierney Elaine E Schmidt Jonathan J Hagopian Louis L Harris Jacqueline J Pevsner Jonathan J

Cold Spring Harbor molecular case studies 20201217 6

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 ...[more]

PMID: 33335013

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Project description:Trisomy 17 is a rare chromosomal disorder. Existing literature on the topic is limited and mostly refer to mosaic Trisomy 17 cases. Our report summarizes the 70-day clinical course of a late preterm neonate with partial Trisomy 17p karyotype 46,XY,der(14)t(14;17)(p11.1;p11.2) dpat. Trisomy 17 due to unbalanced translocation is rare, and our case elaborates the clinical presentation with intestinal malfunction without any anatomical pathology and urethral diverticulum and the ethical dilemma in decision-making. The male proband was born at 35 weeks with antenatal findings of multiple neurological and other abnormalities such as cystic hygroma, absent corpus collosum, high riding third ventricle, absent cavum septum pellucidum, indented occiput, absent ductus venous, and intrauterine growth restriction. The postnatal findings included significant facial dysmorphisms with short palpebral fissures, hypertelorism, low set ears, micrognathia, hirsutism, and single palmar creases, central hypotonia, and hyperreflexia of upper limbs bilaterally. Genital-urinary assessment revealed a urinary diverticulum and significantly underdeveloped scrotum with undescended testes. Infant had excessive irritability and resistance to sleep despite increasing doses of analgesia and sedation, and persistent respiratory and feeding difficulties. Enteral nutrition could not be established due to profuse and persistent diarrhea, necessitating use of total parenteral nutrition. Microarray assay exhibited a pathogenic copy number gain of approximately 21.4 Mb of chromosome region 17p13.3p11.2. Follow-up chromosome analysis and FISH revealed an abnormal male karyotype with a derivative chromosome 14, resulting from an unbalanced translocation between the short arm of one chromosome 14 and the short arm of one chromosome 17, effectively resulting in trisomy 17p11.2. It was derived from a paternal balanced t(14;17)(p11.1;p11.2) as shown by chromosome analysis and FISH studies. The rarity of this chromosomal disorder contributed to difficulty with prognosis and led to bioethical dilemma regarding life-sustaining measures and quality of life. Through shared decision-making processes and in consideration of poor prognosis, parents decided to withdraw life-sustaining care and the proband died at postnatal day of life 70.

Dataset Information

Characterization of an unbalanced translocation causing 3q28qter duplication and 10q26.2qter deletion in a patient with global developmental delay and self-injury.

Publications

Characterization of an unbalanced translocation causing 3q28qter duplication and 10q26.2qter deletion in a patient with global developmental delay and self-injury.

Similar Datasets

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