Mosaic Trisomy 1q Caused by a Novel Unbalanced Structural Rearrangement and Its Mechanism of Origin: A Rare Case of Cytogenetic Anomaly, Congenital Abnormalities, and Neonatal Death

Document Type

Conference Proceeding

Publication Date

11-1-2023

Publication Title

J Mol Diagn

Abstract

Introduction: Trisomy 1q is a rare chromosomal anomaly syndrome (prevalence of < 1/1,000,000) resulting from partial duplication of the long arm of chromosome 1, with a highly variable phenotype. It is an exceedingly rare abnormality with only 12 cases described in the literature, with mos 46,X,der(Y)t(Y;1)(q12;q21) seen in seven cases. Only two resulted in live birth, with longest survival of five months. We herein report a novel unbalanced structural rearrangement resulting in mosaic trisomy 1q and dissected the mechanism of origin. Methods: Genetics was consulted for a female infant with dysmorphic features born to a 28- year-old G2P2 mother and non-consanguineous parents. Blood sample was taken for fluorescence in situ hybridization (FISH), chromosome, and microarray analysis. Variable number tandem repeat (VNTR) analysis and microarray analysis were done to delineate the mechanism of origin. Results: The infant was small for gestational age, had cleft palate, low-set malformed ears, ventriculomegaly, and joint contractures. She was intubated at birth for respiratory distress and eventually expired at 25 days of life due to respiratory complications. FISH results for abnormalities involving chromosomes 13, 18, 21, and sex chromosomes were normal. Chromosome analysis showed duplication of a region of chromosome 1q, which was confirmed using microarray analysis. The patient had mos 46,XX,der(1)t(1;1)(p36.3;q25.2) or mosaic trisomy 1q. Four potential mechanisms can result in this type of genetic alteration: 1) Chimerism; 2) uniparental disomy: begins with an unbalanced zygote, which loses abnormal chromosome 1 and undergoes monosomy rescue, resulting in isodisomy for normal chromosome 1 in a subpopulation of cells; 3) a zygote with two normal chromosome 1 and a derivative chromosome 1 is formed via 3:1 segregation from parent carrying a balanced inversion, and as a result of abnormal cell line's instability, secondary loss of normal chromosome 1 and derivative chromosome 1 occurs, resulting in two different cell lines; 4) a translocation occurs between chromatids during embryogenesis, resulting in either two unbalanced cell lines (one of which was non-viable), or a normal and a balanced cell line. VNTR analysis ruled out chimerism (mechanism 1). Microarray analysis ruled out uniparental disomy (mechanism 2) due to lack of loss of heterozygosity across the entirety of chromosome 1. Mechanism 3 is still a possibility but not likely. We would need to test father’s blood to effectively rule out mechanism 3. Mechanism 4 seems to be the most probable mechanism in this scenario. Conclusions: Here we report a novel genetic alteration leading to mosaic trisomy 1q, which has never been reported in the literature and investigated for its potential mechanism(s) of genesis. These findings are novel and will help in better understanding this rare disease.

Volume

25

Issue

11

First Page

S26

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