2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Quad whole genome sequencing detects reciprocal copy number variants in affected siblings, consistent with familial translocation

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This document presents a case study involving two siblings in Ghana who were evaluated for a neurodevelopmental disorder. The siblings and their parents underwent genome sequencing using the Illumina TruSeq PCR-free kit. The sequencing revealed large copy number variants (CNVs) in both siblings involving chromosomes 3 and 22. Proband 1 had a 10.6 Mb deletion of chromosome 3 and a 7.8 Mb duplication of chromosome 22, while Proband 2 had a 10.6 Mb duplication of chromosome 3 and a 7.8 Mb deletion of chromosome 22.<br />The sequencing also identified unique phenotypic features in each sibling, which were attributed to the chromosomal gains and losses. The analysis indicated that the siblings had reciprocal unbalanced translocations involving 3p26.3-p25.3 and 22q13.2-q13.33. The absence of CNVs in the parents suggested a balanced translocation in one of them, increasing the risk of recurrence in the family.<br />The results were consistent with diagnoses of 3p deletion syndrome and a currently undescribed chromosome 22 duplication phenotype in Proband 1, and partial trisomy 3p syndrome and Phelan-McDermid syndrome in Proband 2. The study highlights the ability of genome sequencing to detect complex structural rearrangements and suggests its potential as a first-line test. It is recommended that karyotyping be performed on the family members to confirm the chromosomal configuration and provide accurate recurrence risk information.<br />This case study demonstrates the expanding capabilities of genome sequencing beyond single nucleotide variants and emphasizes its potential in diagnosing rare and undiagnosed genetic diseases.

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Presenting Author - Katie Golden-Grant, MS, CGC; Co-Author - Amanda Buchanan, MS; Co-Author - Alison J. Coffey, PhD; Co-Author - Brittany Thomas, MS, CGC; Co-Author - Yvonne Brew, MD; Co-Author - Akanchha Kesari; Co-Author - Denise L. Perry, MS; Co-Author - Ryan J. Taft, PhD;

Meta Tag

Chromosomal Abnormalities

Etiology

Genetic Testing

Genomic Methodologies

Intellectual disability

Methodology

NextGen Sequencing

Phenotype

Sequencing

Variant Detection

Co-Author Amanda Buchanan, MS

Co-Author Alison J. Coffey, PhD

Co-Author Brittany Thomas, MS, CGC

Co-Author Yvonne Brew, MD

Co-Author Akanchha Kesari

Co-Author Denise L. Perry, MS

Co-Author Ryan J. Taft, PhD

Presenting Author Katie Golden-Grant, MS, CGC

Keywords

neurodevelopmental disorder

genome sequencing

copy number variants

chromosomes 3 and 22

phenotypic features

reciprocal unbalanced translocations

3p deletion syndrome

chromosome 22 duplication phenotype

partial trisomy 3p syndrome

rare genetic diseases