Prenatal diagnosis of a fetus with megacystis and monosomy 21

Chang, Ling; Chen, Pei Yi; Kuo, Pao Lin; Chang, Feng-Cheng

doi:10.1002/pd.86

Cited by 14 publications

(10 citation statements)

References 5 publications

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“…As predicted, we obtained Dp(16)1Yey/Df(16)2Yey progeny from this cross, providing evidence that the Tiam1-Kcnj6 region contains a gene(s) associated with haploinsufficient lethality. This gene(s) may underlie the embryonic lethality associated with human monosomy 21 (Chang et al 2001; Joosten et al 1997). The duplication was designated as Dup(16Tiam1-Kcnj6)Yey , abbreviated as Dp(16)2Yey or Ts4Yey.…”

Section: Resultsmentioning

confidence: 99%

Genetic analysis of Down syndrome-associated heart defects in mice

Liu

Morishima

et al. 2011

Hum Genet

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Human trisomy 21, the chromosomal basis of Down syndrome (DS), is the most common genetic cause of heart defects. Regions on human chromosome 21 (Has21) are syntenically conserved with three regions located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. In this study, we have analyzed the impact of duplications of each syntenic region on cardiovascular development in mice and have found that only the duplication on Mmu16, i.e., Dp(16)1Yey, is associated with heart defects. Furthermore, we generated two novel mouse models carrying a 5.43-Mb duplication and a reciprocal deletion between Tiam1 and Kcnj6 using chromosome engineering, Dp(Tiam1-Kcnj6)Yey/+ and Df(Tiam1-Kcnj6)Yey/+, respectively, within the 22.9-Mb syntenic region on Mmu16. We found that Dp(Tiam1-Kcnj6)Yey/+, but not Dp(16)1Yey/Df(Tiam1-Kcnj6)Yey, resulted in heart defects, indicating that triplication of the Tiam1-Knj6 region is necessary and sufficient to cause DS-associated heart defects. Our transcriptional analysis of Dp(Tiam1-Kcnj6)Yey/+ embryos confirmed elevated expression levels for the genes located in the Tiam-Kcnj6 region. Therefore, we established the smallest critical genomic region for DS-associated heart defects to lay the foundation for identifying the causative gene(s) for this phenotype.

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Section: Resultsmentioning

confidence: 99%

Genetic analysis of Down syndrome-associated heart defects in mice

Liu

Morishima

et al. 2011

Hum Genet

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“…As predicted, we obtained Dp(16)1Yey/Df(16)4Yey progeny from this cross, providing evidence that the Ifnar1-Kcnj6 region contains a gene(s) associated with haploinsufficient lethality. This gene(s) may underlie the embryonic lethality associated with human monosomy 21 (Chang et al 2001; Joosten et al 1997). The duplication was designated as Dup(16Ifnar1-Kcnj6)Yey , abbreviated as Dp(16)4Yey or Ts6Yey.…”

Section: Resultsmentioning

confidence: 99%

Engineered chromosome-based genetic mapping establishes a 3.7 Mb critical genomic region for Down syndrome-associated heart defects in mice

et al. 2013

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Trisomy 21 (Down syndrome, DS) is the most common human genetic anomaly associated with heart defects. Based on evolutionary conservation, DS-associated heart defects have been modeled in mice. By generating and analyzing mouse mutants carrying different genomic rearrangements in human chromosome 21 (Hsa21) syntenic regions, we found the triplication of the Tiam1-Kcnj6 region on mouse chromosome 16 (Mmu16) resulted in DS-related cardiovascular abnormalities. In this study, we developed two tandem duplications spanning the Tiam1-Kcnj6 genomic region on Mmu16 using recombinase-mediated genome engineering, Dp(16)3Yey and Dp(16)4Yey, spanning the 2.1Mb Tiam1-Il10rb and 3.7Mb Ifnar1-Kcnj6 regions, respectively. We found that Dp(16)4Yey/+, but not Dp(16)3Yey/+, led to heart defects, suggesting the triplication of the Ifnar1-Kcnj6 region is sufficient to cause DS-associated heart defects. Our transcriptional analysis of Dp(16)4Yey/+ embryos showed that the Hsa21 gene orthologs located within the duplicated interval were expressed at the elevated levels, reflecting the consequences of the gene dosage alterations. Therefore, we have identified a 3.7Mb genomic region, the smallest critical genomic region, for DS-associated heart defects, and our results should set the stage for the final step to establish the identities of the causal gene(s), whose elevated expression(s) directly underlie this major DS phenotype.

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“…In addition, some prenatal cases without molecular confirmation were also reported [Ghidini et al, 1993;Chang et al, 2001].…”

Section: Introductionmentioning

confidence: 91%

A prenatally diagnosed patient with full monosomy 21: Ultrasound, cytogenetic, clinical, molecular, and necropsy findings

Mori

Lapunzina

Delicado

et al. 2003

American J of Med Genetics Pt A

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We report on a patient with a full monosomy 21 (FM21) prenatally diagnosed in cord fetal blood, and subsequently confirmed in other tissues. Subtle chromosomal translocations of chromosome 21, were ruled-out by FISH using both painting and 21q telomeric probes. Microsatellites analysis demonstrated the paternal origin of the single chromosome. The propositus showed at 32 weeks of gestation a severe intrauterine growth retardation and microcephaly. He was born with multiple congenital malformations, hypotonia, microcephaly, bilateral microphthalmia (more severe on the left), facial dysmorphism, agenesis of the external auditory meatus, redundant skin in the neck, narrow chest, flat scrotum, cryptorchydism, hypospadias, micropene, camptodactyly, nail hypoplasia, and abnormal palmar and plantar creases. The patient died in the first day of life. At necropsy, micrencephaly, semilobar holoprosencephaly, polimicrogyria, ocular abnormalities, skeletal anomalies, congenital heart disease, and agenesis of right kidney were also observed. To our best knowledge, this case is one of the most completely patient studied with FM21.

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Prenatal diagnosis of a fetus with megacystis and monosomy 21

Abstract: Figure 1-Sonography of the fetus at 13 weeks' gestation; the crown-rump length measured 7.4 cm and the bladder measured 1.1r1.7 cm (arrow) PRENATAL DIAGNOSIS Prenat Diagn 2001; 21: 512-513.

Cited by 14 publications

References 5 publications

Genetic analysis of Down syndrome-associated heart defects in mice

Genetic analysis of Down syndrome-associated heart defects in mice

Engineered chromosome-based genetic mapping establishes a 3.7 Mb critical genomic region for Down syndrome-associated heart defects in mice

A prenatally diagnosed patient with full monosomy 21: Ultrasound, cytogenetic, clinical, molecular, and necropsy findings

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