PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Meier-Gorlin Syndrome: Clinical Misdiagnosis as Jeune Syndrome, Genetic Testing and Functional Analysis of ORC6 Mutations and the Development of a Prenatal Test
Version 1
: Received: 20 May 2022 / Approved: 23 May 2022 / Online: 23 May 2022 (10:18:24 CEST)
How to cite:
Nazarenko, M. S.; Viakhireva, I. V.; Skoblov, M. Y.; Soloveva, E. V.; Sleptcov, A. A.; Nazarenko, L. P. Meier-Gorlin Syndrome: Clinical Misdiagnosis as Jeune Syndrome, Genetic Testing and Functional Analysis of ORC6 Mutations and the Development of a Prenatal Test. Preprints2022, 2022050292. https://doi.org/10.20944/preprints202205.0292.v1
Nazarenko, M. S.; Viakhireva, I. V.; Skoblov, M. Y.; Soloveva, E. V.; Sleptcov, A. A.; Nazarenko, L. P. Meier-Gorlin Syndrome: Clinical Misdiagnosis as Jeune Syndrome, Genetic Testing and Functional Analysis of ORC6 Mutations and the Development of a Prenatal Test. Preprints 2022, 2022050292. https://doi.org/10.20944/preprints202205.0292.v1
Nazarenko, M. S.; Viakhireva, I. V.; Skoblov, M. Y.; Soloveva, E. V.; Sleptcov, A. A.; Nazarenko, L. P. Meier-Gorlin Syndrome: Clinical Misdiagnosis as Jeune Syndrome, Genetic Testing and Functional Analysis of ORC6 Mutations and the Development of a Prenatal Test. Preprints2022, 2022050292. https://doi.org/10.20944/preprints202205.0292.v1
APA Style
Nazarenko, M. S., Viakhireva, I. V., Skoblov, M. Y., Soloveva, E. V., Sleptcov, A. A., & Nazarenko, L. P. (2022). Meier-Gorlin Syndrome: Clinical Misdiagnosis as Jeune Syndrome, Genetic Testing and Functional Analysis of ORC6 Mutations and the Development of a Prenatal Test. Preprints. https://doi.org/10.20944/preprints202205.0292.v1
Chicago/Turabian Style
Nazarenko, M. S., Aleksei A. Sleptcov and Ludmila P. Nazarenko. 2022 "Meier-Gorlin Syndrome: Clinical Misdiagnosis as Jeune Syndrome, Genetic Testing and Functional Analysis of ORC6 Mutations and the Development of a Prenatal Test" Preprints. https://doi.org/10.20944/preprints202205.0292.v1
Abstract
Meier–Gorlin syndrome (MGS) is a rare genetic developmental disorder that causes primordial proportional dwarfism, microtia, absent or hypoplastic patellae and other skeletal anomalies. Overlapping skeletal symptoms make MGS difficult to diagnose clinically. We describe a 3-year-old boy with short stature, recurrent respiratory infections, short-rib dysplasia, tower head and facial dysmorphisms who was admitted to the Tomsk Genetic Clinic to verify a clinical diagnosis of Jeune syndrome. Clinical Exome sequencing revealed two variants (compound heterozygosity) in the ORC6 gene: c.2T>C(p.Met1Thr) and c.449+5G>A. In silico analysis showed the pathogenicity of these two mutations and predicted a decrease in donor splicing site strength for c.449+5G>A. An in vitro minigene assay demonstrated that variant c.449+5G>A causes a complete skipping of exon 4 in ORC6 gene. The parents asked for urgent prenatal testing for MGS for the next pregnancy, but it ended in a miscarriage. Thus, this case report may help to prevent MGS misdiagnosis in the future. We also performed in silico and functional analyses of ORC6 mutations and developed a restriction fragment length polymorphism and haplotype-based short-tandem-repeat assay for prenatal genetic testing for MGS. These findings should elucidate MGS aetiology and improve the quality of genetic counselling for affected families.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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