2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-A 7.4 Mb Duplication of 6p22.1-22.3 in a Cognitively Normal Adult with a History of Multiple Congenital Anomalies

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This document presents a case study of a 29-year-old man who has normal cognitive abilities but a history of multiple congenital anomalies. The man exhibits features such as hypertelorism (widely spaced eyes) and downslanting right eye, bilateral ptosis (drooping eyelids), high forehead, scoliosis, and a history of academic excellence. Genetic investigations did not reveal any variants in genes that could explain his phenotype. However, exome copy number variant (CNV) calling identified a duplication of approximately 7.4 Mb on chromosome 6p22.1-22.3. The duplicated region includes various genes, pseudogenes, tRNA genes, and non-coding RNAs. Further steps include re-evaluating the karyotype, performing sequencing to identify the duplication breakpoints and their potential effects on genes, and comparing findings with another individual who has a similar genotype and phenotype. The DECIPHER database does not currently have any overlapping individuals with this duplication. The features observed in the case are consistent with Saethre-Chotzen or Opitz G/BBB syndromes, and the 6p22.1-22.3 duplication is believed to be the best explanation for the congenital anomalies seen in this individual and the other similar case. Studies on chromosome 6p CNVs typically describe larger regions or unbalanced translocations involving other chromosomes with cognitive involvement, making these cases unique. Notably, none of the genes in the duplicated region are known or predicted to be triplo-sensitive. Overall, the 6p22.1-22.3 duplication is believed to be the underlying cause of the observed congenital anomalies in these individuals.

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Presenting Author - Andrew K. Sobering, PhD; Co-Author - Victor Keesee, MD; Co-Author - Yasseen Amellal, BSc; Co-Author - Sarah H. Elsea, PhD, FACMG; Co-Author - Dong Li, PhD; Co-Author - Elizabeth J. Bhoj, MD, PhD;

Meta Tag

Chromosomal Abnormalities

Congenital Anomaly

Dysmorphology

Co-Author Victor Keesee, MD

Co-Author Yasseen Amellal, BSc

Co-Author Sarah H. Elsea, PhD, FACMG

Co-Author Dong Li, PhD

Co-Author Elizabeth J. Bhoj, MD, PhD

Presenting Author Andrew K. Sobering, PhD

Keywords

case study

29-year-old man

normal cognitive abilities

congenital anomalies

hypertelorism

downslanting right eye

ptosis

high forehead

scoliosis

academic excellence