Prenatal diagnosis of Proteus syndrome: Diagnosis of an <scp><i>AKT1</i></scp> mutation from amniocytes

Abell, Katherine; Tolusso, Leandra; Smith, Nicki Mclaurin; Hopkin, Robert J.; Vawter-Lee, Marissa; Habli, Mounira; Riddle, Stefanie; Calvo-Garcia, Maria A.; Guan, Qiaoning; Bierbrauer, Karin; Hwa, Vivian; Saal, Howard M.

doi:10.1002/bdr2.1801

Cited by 6 publications

(3 citation statements)

References 16 publications

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“…Second, somatic mosaicism is easily missed due to the limitation in sampling tissue and detection method [ 23 ]. Third, mosaicism may evolve over time with changes in the percentages of normal and abnormal cells [ 24 ]. Genome-wide screening methods, such as chromosomal microarray, have been widely used in pediatric genetics and have increased the diagnostic yield for mosaic chromosomal disorders.…”

Section: Discussionmentioning

confidence: 99%

Characterization of a rare mosaic unbalanced translocation of t(3;12) in a patient with neurodevelopmental disorders

Baker

Johnson

et al. 2022

Mol Cytogenet

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Background Unbalanced translocations may be de novo or inherited from one parent carrying the balanced form and are usually present in all cells. Mosaic unbalanced translocations are extremely rare with a highly variable phenotype depending on the tissue distribution and level of mosaicism. Mosaicism for structural chromosomal abnormalities is clinically challenging for diagnosis and counseling due to the limitation of technical platforms and complex mechanisms, respectively. Here we report a case with a tremendously rare maternally-derived mosaic unbalanced translocation of t(3;12), and we illustrate the unreported complicated mechanism using single nucleotide polymorphism (SNP) array, fluorescence in situ hybridization (FISH), and chromosome analyses. Case presentation An 18-year-old female with a history of microcephaly, pervasive developmental disorder, intellectual disability, sensory integration disorder, gastroparesis, and hypotonia presented to our genetics clinic. She had negative karyotype by parental report but no other genetic testing performed previously. SNP microarray analysis revealed a complex genotype including 8.4 Mb terminal mosaic duplication on chromosome 3 (3p26.3->3p26.1) with the distal 5.7 Mb involving two parental haplotypes and the proximal 2.7 Mb involving three parental haplotypes, and a 6.1 Mb terminal mosaic deletion on chromosome 12 (12p13.33->12p13.31) with no evidence for a second haplotype. Adjacent to the mosaic deletion is an interstitial mosaic copy-neutral region of homozygosity (1.9 Mb, 12p13.31). The mother of this individual was confirmed by chromosome analysis and FISH that she carries a balanced translocation, t(3;12)(p26.1;p13.31). Conclusion Taken together, the proband, when at the stage of a zygote, likely carried the derivative chromosome 12 from this translocation, and a postzygotic mitotic recombination event occurred between the normal paternal chromosome 12 and maternal derivative chromosome 12 to “correct” the partial 3p trisomy and partial deletion of 12p. To the best of our knowledge, it is the first time to report the mechanism utilizing a combined cytogenetic and cytogenomic approach, and we believe it expands our knowledge of mosaic structural chromosomal disorders and provides new insight into clinical management and genetic counseling.

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Section: Discussionmentioning

confidence: 99%

Characterization of a rare mosaic unbalanced translocation of t(3;12) in a patient with neurodevelopmental disorders

Baker

Johnson

et al. 2022

Mol Cytogenet

Self Cite

View full text Add to dashboard Cite

show abstract

“…Second, somatic mosaicism is easily missed due to the limitation in sampling tissue and detection method [19]. Third, mosaicism may evolve over time with changes in the percentages of normal and abnormal cells [20]. Genome-wide screening methods, such as chromosomal microarray, have been widely used in pediatric genetics and have increased the diagnostic yield for mosaic chromosomal disorders.…”

Section: Discussionmentioning

confidence: 99%

Characterization of a Rare Mosaic Unbalanced Translocation of t(3;12) in a Patient With Neurodevelopmental Disorders

Baker

Johnson

et al. 2021

Preprint

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Background Unbalanced translocations may be de novo or inherited from one parent carrying the balanced form and are usually present in all cells. Mosaic unbalanced translocations are extremely rare with a highly variable phenotype depending on the tissue distribution and level of mosaicism. Mosaicism for structural chromosomal abnormalities is clinically challenging for diagnosis and counseling due to the limitation of technical platforms and complex mechanisms, respectively. Here we report a case with a tremendously rare maternally-derived mosaic unbalanced translocation of t(3;12), and we illustrate the unreported complicated mechanism using single nucleotide polymorphism (SNP) array, fluorescence in situ hybridization (FISH), and chromosome analyses. Case Presentation: An 18-year-old female with a history of microcephaly, pervasive developmental disorder, intellectual disability, sensory integration disorder, gastroparesis, and hypotonia presented to our genetics clinic. She had negative karyotype by parental report but no other genetic testing performed previously. SNP microarray analysis revealed a complex genotype including 8.4 Mb terminal mosaic duplication on chromosome 3 (3p26.3->3p26.1) with the distal 5.7 Mb involving two parental haplotypes and the proximal 2.7 Mb involving three parental haplotypes, and a 6.1 Mb terminal mosaic deletion on chromosome 12 (12p13.33->12p13.31) with no evidence for a second haplotype. Adjacent to the mosaic deletion is an interstitial mosaic copy-neutral region of homozygosity (1.9 Mb, 12p13.31). The mother of this individual was confirmed by chromosome analysis and FISH that she carries a balanced translocation, t(3;12)(p26.1;p13.31). Conclusion Taken together, the proband, when at the stage of a zygote, likely carried the derivative chromosome 12 from this translocation, and a postzygotic mitotic recombination event occurred between the normal paternal chromosome 12 and maternal derivative chromosome 12 to “correct” the partial 3p trisomy and partial deletion of 12p. To the best of our knowledge, it is the first time that a mechanism utilizing a combined cytogenetic and cytogenomic approach, and we believe it expands our knowledge of mosaic structural chromosomal disorders and provides new insight into clinical management and genetic counseling.

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“…With developments in genetic studies, we now have facilities to detect AKT1 pathogenic variant in cultured amniocytes in suspected fetuses with segmental overgrowth, skeletal and CNS abnormalities (11).…”

Section: General Criteria Specific Criteriamentioning

confidence: 99%

A case of Proteus syndrome with a large atrial septal defect

Kariyawasam¹,

Kankananarachchi²,

Naotunna³

et al. 2021

Galle Med J

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Prenatal diagnosis of Proteus syndrome: Diagnosis of an AKT1 mutation from amniocytes

Cited by 6 publications

References 16 publications

Characterization of a rare mosaic unbalanced translocation of t(3;12) in a patient with neurodevelopmental disorders

Characterization of a rare mosaic unbalanced translocation of t(3;12) in a patient with neurodevelopmental disorders

Characterization of a Rare Mosaic Unbalanced Translocation of t(3;12) in a Patient With Neurodevelopmental Disorders

A case of Proteus syndrome with a large atrial septal defect

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