A novel genetic variant in loss of heterozygosity

L. Thulasi Devi

doi:10.18203/2320-1770.ijrcog20260911

Authors

L. Thulasi Devi Department of Obstetrics and Gynaecology, Military Hospital, Nasirabad, Rajasthan, India https://orcid.org/0000-0002-4607-7797

DOI:

https://doi.org/10.18203/2320-1770.ijrcog20260911

Keywords:

LOH, BOH, Consanguinity, Human evolution, Obstetric surveillance, Medical genetics, Genetic screening, MTP services, OMIM

Abstract

An interesting case of loss of heterozygosity (LOH) and BOH with a history of second degree consanguineous marriage with manifestation of congenital fetal malformation in all her previous pregnancies. A case of missed clinical diagnosis and poor correlation of available clues and data due to lack of awareness, poor history taking and repeated irrelevant investigations, relying mostly on sonography and adhocism. This case is being reported as consanguinity is extremely widespread in the subcontinent and patients seldom get answers to recurrent miscarriages and fetal loss. On evaluation, the affected fetus had novel – likely pathogenic genetic variant not yet classified.

References

Naeim F, Rao PN, Grody WW. Chapter 3 - Principles of Cytogenetics, Hematopathology. Academic Press. 2008;57-64. DOI: https://doi.org/10.1016/B978-0-12-370607-2.00003-X

Schwab M. Loss of Heterozygosity. Encyclopedia of Cancer. Springer, Berlin, Heidelberg. 2011.

Ryland GL, Doyle MA, Goode D, Boyle SE, Choong DYH, Rowley SM, et al. Loss of heterozygosity: what is it good for? BMC Med Genomics. 2015;8:45. DOI: https://doi.org/10.1186/s12920-015-0123-z

McGowan-Jordan J, Hastings R, Moore S. Re: International System for Human Cytogenetic or Cytogenomic Nomenclature (ISCN): Some Thoughts. Cytogenetic Genome Res. 2021;161(5):225-6. DOI: https://doi.org/10.1159/000516655

Hoppman N, Rumilla K, Lauer E, Kearney H, Thorland E. Patterns of homozygosity in patients with uniparental disomy: detection rate and suggested reporting thresholds for SNP microarrays. Genet Med. 2018;20(12):1522-7. DOI: https://doi.org/10.1038/gim.2018.24

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-24. DOI: https://doi.org/10.1038/gim.2015.30

Behera S, Catreux S, Rossi M, Truong S, Huong Z, Ruehle M, et al., Comprehensive genome analysis and variant detection at scale using DRAGEN, Nat Biotechnol 2024;2382. DOI: https://doi.org/10.1038/s41587-024-02382-1

Lee K, Abul-Husn NS, Amendola LM, Brothers KB, Chung WK, Gollob MS, et al. ACMG SF v3.3 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2025;27(8):101454. DOI: https://doi.org/10.1016/j.gim.2025.101454

Amberger JS, Bocchini CA, Schiettecatte F, Scott AF, Hamosh A. OMIM.org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders. Nucleic Acids Res. 2015;43:D789-98. DOI: https://doi.org/10.1093/nar/gku1205

Landrum MJ, Chitipiralla S, Brown GR, Chen C, Gu B, Hart J, et al. ClinVar: improvements to accessing data. Nucleic Acids Res. 2020;48(D1):D835-44. DOI: https://doi.org/10.1093/nar/gkz972

Rehder C, Bean LJH, Bick D, Chao E, Chung W, Das S, et al. Next-generation sequencing for constitutional variants in the clinical laboratory, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021;23(8):1399-415. DOI: https://doi.org/10.1038/s41436-021-01139-4

Stelzer G, Rosen R, Plaschkes I, Zimmerman S, Twik M, Fishilevich S, et al. The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses. Curr Protocols Bioinformat. 2016;54:30-3. DOI: https://doi.org/10.1002/cpbi.5

Rappaport N, Twik M, Plaschkes I, Nudel R, Stein TI, Levitt J, et al. MalaCards: an amalgamated human disease compendium with diverse clinical and genetic annotation and structured search. Nucleic Acid Res. 2017;45(D1):D877-87. DOI: https://doi.org/10.1093/nar/gkw1012

Jeffries L, Mis EK, McWalter K, Donkervoort S, Brodsky NN, Carpier J-M, et al. Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections. Genet Med. 2024;26(2):101023. DOI: https://doi.org/10.1016/j.gim.2023.101023

MalaCards-Human Disease Database. Atrio-ventricular Septal Defect (AVSD). Available at: https://www.malacards.org/card/atrioventricular_septal_defect?search=CRELD1#TraitsCategories. Accessed on 12 January 2026.