A rare case of postnatal mosaic trisomy 12 with severe congenital heart disease and literature review

Hu, Xiaolin; Ayala, Sofia Saenz; Dyer, Lisa M.; Guan, Qiaoning; Peña, Loren

doi:10.1002/ajmg.a.62166

Cited by 5 publications

(6 citation statements)

References 36 publications

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“…Previously, we demonstrated the clinical utility of using SNP microarray in detecting rare mosaic chromosomal disorders [11,12]. Here, we discuss the utility of SNP microarray in determining the complex origin of a mosaic unbalanced translocation.…”

Section: Discussionmentioning

confidence: 99%

“…A meiotic recombination event occurred between the normal 3p and the derivative 12 harboring the translocated 3p. The recombination site on der (12) was distal to the breakpoint of the balanced t(3;12) ( gure 2a). Fertilization of the oocyte with a "normal" recombinant chromosome 3 and der( 12) by a sperm containing normal chromosomes 3 and 12 resulted in a zygote with an 8.4 Mb duplication of 3p26.3->3p26.1 ( gure 2b, cell line 1).…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…Previously, we demonstrated the clinical utility of using SNP microarray in detecting rare mosaic chromosomal disorders [ 11 , 14 ]. Here, we discuss the utility of SNP microarray in determining the complex origin of a mosaic unbalanced translocation.…”

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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“…All these alterations are not common features in patients previously described in the literature (Table 2 ) [ 8 ]. Because a clinical hallmark of facial dysmorphism has not yet been described for patients with mosaic trisomy 12, the definition of this entity as “Mosaic Trisomy 12 Syndrome” has not been possible [ 6 , 7 , 15 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…In comparison, 7/21 previously reported patients with mosaic trisomy 12 showed pigmentary manifestations, described only as patchy or linear streaks [ 13 , 15 , 17 ]. Unfortunately, only in 3 of the total previously reported cases, a detailed description of the pigmentation pattern with disseminated dermatosis following Blaschko lines was described (Table 2 ) [ 5 – 7 ].…”

Section: Discussionmentioning

confidence: 99%

Pigmentary mosaicism as a recurrent clinical manifestation in three new patients with mosaic trisomy 12 diagnosed postnatally: cases report and literature review

et al. 2022

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Background To date, only twenty-one cases diagnosed postnatally with mosaic trisomy 12 have been reported. The most frequent phenotypic manifestations are developmental delay, dysmorphic facial features, congenital heart defects, digital alterations, and pigmentary disorders. In the present report, detailed clinical and genetic profiles of three unrelated new patients with mosaic trisomy 12 are described and compared with previously reported cases. Case presentation In the present report, we include the clinical, cytogenetic, and molecular description of three Mexican patients diagnosed postnatally with mosaic trisomy 12. At phenotypic level, the three patients present with developmental delay, dysmorphic facial features, congenital heart defects and skin pigmentary anomalies. Particularly, patient 1 showed unique eye alterations as bilateral distichiasis, triple rows of upper lashes, and digital abnormalities. In patient 2 redundant skin, severe hearing loss, and hypotonia were observed, and patient 3 presented with hypertelorism and telecanthus. Hyperpigmentation with disseminated pigmentary anomalies is a common trait in all of them. The cytogenetic study was carried out under the strict criteria of analysis, screening 50–100 metaphases from three different tissues, showing trisomy 12 mosaicism in at least one of the three different tissues analyzed. With SNParray, the presence of low-level mosaic copy number variants not previously detected by cytogenetics, and uniparental disomy of chromosome 12, was excluded. STR markers allowed to confirm the absence of uniparental disomy as well as to know the parental origin of supernumerary chromosome 12. Conclusions The detailed clinical, cytogenetic, and molecular description of these three new patients, contributes with relevant information to delineate more accurately a group of patients that show a heterogeneous phenotype, although sharing the same chromosomal alteration. The possibility of detecting mosaic trisomy 12 is directly associated with the sensitivity of the methodology applied to reveal the low-level chromosomal mosaicism, as well as with the possibility to perform the analysis in a suitable tissue.

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A rare case of postnatal mosaic trisomy 12 with severe congenital heart disease and literature review

Cited by 5 publications

References 36 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

Pigmentary mosaicism as a recurrent clinical manifestation in three new patients with mosaic trisomy 12 diagnosed postnatally: cases report and literature review

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