Prenatal Diagnosis of a Mosaic Paternal Uniparental Disomy for Chromosome 14: A Case Report of Kagami–Ogata Syndrome

The Kagami–Ogata syndrome (KOS) is a rare imprinting disorder with a distinct clinical phenotype. In KOS, polyhydramnios is associated with a small bell-shaped thorax and coat-hanger ribs. The genetic etiology of KOS includes paternal uniparental disomy 14 [upd(14)pat], epimutations, and microdeletions affecting the maternally derived imprinted region of chromosome 14q32.2. More than 77 cases of KOS have been reported; however, only one mosaic upd(14)pat case has been reported. Here we report a second mosaic upd(14)pat case. The prognosis of upd(14)pat patients is poor because of severe respiratory insufficiency. We summarized prenatal ultrasound findings of KOS to raise awareness of this condition for possible diagnosis of KOS prenatally when polyhydramnios combination with a small bell-shaped thorax and other related features are first observed. Prenatal diagnosis using methylation-specific multiplex ligation-dependent probe amplification (MLPA) or a single-nucleotide polymorphism-based microarray analysis is recommended.

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Prenatal diagnosis of paternal uniparental disomy for chromosome 14 using a single-nucleotide-polymorphism-based microarray analysis: A case report

Journal of the Formosan Medical Association ◽

10.1016/j.jfma.2018.12.010 ◽

2019 ◽

Vol 118 (3) ◽

pp. 739-742 ◽

Cited By ~ 2

Author(s):

Chih-Ling Chen ◽

Chien-Nan Lee ◽

Ming-Wei Lin ◽

Wen-Wei Hsu ◽

Yi-Yun Tai ◽

...

Keyword(s):

Single Nucleotide Polymorphism ◽

Case Report ◽

Prenatal Diagnosis ◽

Microarray Analysis ◽

Uniparental Disomy ◽

Nucleotide Polymorphism ◽

Chromosome 14 ◽

Single Nucleotide ◽

Paternal Uniparental Disomy

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Prenatal diagnosis of 7 cases with uniparental disomy by utilization of single nucleotide polymorphism array

Molecular Cytogenetics ◽

10.1186/s13039-021-00537-2 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Lili Zhou ◽

Zhaoke Zheng ◽

Yunzhi Xu ◽

Xiaoxiao Lv ◽

Chenyang Xu ◽

...

Keyword(s):

Single Nucleotide Polymorphism ◽

Prenatal Diagnosis ◽

Molecular Analysis ◽

Correct Diagnosis ◽

Snp Array ◽

Uniparental Disomy ◽

Chromosome 1 ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Rescue Mechanism

Abstract Background The phenotypes of uniparental disomy (UPD) are variable, which may either have no clinical impact, lead to clinical signs and symptoms. Molecular analysis is essential for making a correct diagnosis. This study involved a retrospective analysis of 4512 prenatal diagnosis samples and explored the molecular characteristics and prenatal phenotypes of UPD using a single nucleotide polymorphism (SNP) array. Results Out of the 4512 samples, a total of seven cases of UPD were detected with an overall frequency of 0.16%. Among the seven cases of UPD, two cases are associated with chromosomal aberrations (2/7), four cases (4/7) had abnormal ultrasonographic findings. One case presented with iso-UPD (14), and two case presented with mixed hetero/iso-UPD (15), which were confirmed by Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) as maternal UPD (15) associated with Prader-Willi syndrome (PWS). Four cases had iso-UPD for chromosome 1, 3, 14, and 16, respectively; this is consistent with the monosomy rescue mechanism. Another three cases presented with mixed hetero/isodisomy were consistent with a trisomy rescue mechanism. Conclusion The prenatal phenotypes of UPD are variable and molecular analysis is essential for making a correct diagnosis and genetic counselling of UPD. The SNP array is a useful genetic test in prenatal diagnosis cases with UPD.

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P11.15: Prenatal ultrasound findings in a fetus with paternal uniparental disomy 14: the “coat-hanger” sign as a diagnostic clue

Ultrasound in Obstetrics and Gynecology ◽

10.1002/uog.1542 ◽

2004 ◽

Vol 24 (3) ◽

pp. 332-332

Author(s):

E. Antonelli ◽

L. Curtis ◽

P. Rimensberger ◽

S. Fokstuen ◽

O. Irion ◽

...

Keyword(s):

Uniparental Disomy ◽

Prenatal Ultrasound ◽

Ultrasound Findings ◽

Paternal Uniparental Disomy ◽

Diagnostic Clue ◽

Uniparental Disomy 14

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Prenatal diagnosis of 22q11.2 copy number abnormalities in fetuses via single nucleotide polymorphism array

Molecular Biology Reports ◽

10.1007/s11033-020-05815-7 ◽

2020 ◽

Vol 47 (10) ◽

pp. 7529-7535

Author(s):

Meiying Cai ◽

Na Lin ◽

Linjuan Su ◽

Xiaoqing Wu ◽

Xiaorui Xie ◽

...

Keyword(s):

Single Nucleotide Polymorphism ◽

Prenatal Diagnosis ◽

Copy Number ◽

Single Nucleotide Polymorphism Array ◽

Snp Array ◽

Cardiovascular Malformations ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Ultrasound Findings ◽

Kidney Malformations

Abstract The q11.2 region on chromosome 22 contains numerous low-copy repeats that lead to deleted or duplicated regions in the chromosome, thereby resulting in different syndromes characterized by intellectual disabilities or congenital anomalies. The association between patient phenotypes and 22q11.2 copy number abnormalities has been previously described in postnatal cases; however, these features have not been systematically evaluated in prenatal cases because of limitations in phenotypic identification in prenatal testing. In this study, we investigated the detection rate of 22q11.2 copy number abnormalities in 2500 fetuses using single nucleotide polymorphism (SNP) array and determined the common abnormal ultrasound findings in fetuses carrying the 22q11.2 copy number abnormalities. The 22q11.2 copy number abnormalities were identified in 13 fetuses with cardiovascular malformations (6/13), kidney malformations (3/13), isolated ultrasound markers (3/13), or high-risk Down syndrome based on maternal serum screening (1/13). Approximately 0.5% (13/2500) of the fetuses harbored 22q11.2 copy number abnormalities. The most frequent ultrasound findings in fetuses with these abnormalities were cardiovascular malformations, followed by kidney malformations and isolated ultrasound markers. Prenatal diagnosis of these genetic abnormalities allows for the delineation of differential diagnoses, characterization of a wide spectrum of associated malformations, and determination of associations that exist between prenatal diagnosis and obstetrical outcomes.

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Paternal Uniparental Disomy of Chromosome 14 with Hypospadias

Cytogenetic and Genome Research ◽

10.1159/000446783 ◽

2016 ◽

Vol 148 (4) ◽

pp. 256-261 ◽

Cited By ~ 2

Author(s):

Haiming Yuan ◽

Yingjun Xie ◽

Qian Li ◽

Xizi Hu ◽

Xinwei Li ◽

...

Keyword(s):

Uniparental Disomy ◽

Normal Karyotype ◽

Nucleotide Polymorphisms ◽

Chromosome 14 ◽

Single Nucleotide ◽

Increased Risk ◽

Specific Configuration ◽

Paternal Uniparental Disomy ◽

Uniparental Disomy 14 ◽

Genetic Phenomenon

Paternal uniparental disomy 14 (patUPD14) is a distinct, clinically recognizable syndrome. Using a clinical SNP microarray, we identified patUPD14 in a boy with a normal karyotype presenting cardiomyopathy and facial anomalies, a specific configuration of the thoracic ribs (‘coat hanger sign'), and hypospadias. Analyses of polymorphic microsatellites confirmed the diagnosis of patUPD14. We discuss the functions of the genes included in the rearrangement and their involvement in the pathogenesis of these disorders, especially hypospadias. ESR2 single nucleotide polymorphisms (rs944050; 2681-4A>G) have been associated with an increased risk of hypospadias in previous studies. The patient's ESR2 (rs944050) genotype is GG, whereas the parents both exhibit an AG genotype. This report sheds light on the genetic phenomenon in which the combination of a polymorphism and UPD can lead to new phenotypes, such as hypospadias.

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The Efficiency of SNP-Based Microarrays in the Detection of Copy-Neutral Events at 15q11.2 and 11p15.5 Loci

Journal of Pediatric Genetics ◽

10.1055/s-0039-1698420 ◽

2019 ◽

Vol 09 (01) ◽

pp. 009-018

Author(s):

Berk Ozyilmaz ◽

Ozgur Kirbiyik ◽

Taha R. Ozdemir ◽

Ozge Ozer Kaya ◽

Yasar B. Kutbay ◽

...

Keyword(s):

Single Nucleotide Polymorphism ◽

False Negative ◽

Uniparental Disomy ◽

Evaluation Process ◽

Aberrant Methylation ◽

Nucleotide Polymorphism ◽

Methylation Analysis ◽

Single Nucleotide ◽

Snp Microarray ◽

Dependent Probe

AbstractPrader–Willi, Angelman, Beckwith–Wiedemann, and Russell–Silver are imprinting syndromes. In this study, we aimed to compare the efficiency of single nucleotide polymorphism (SNP) microarray analysis with methylation-specific Multiplex ligation-dependent probe amplification (MS-MLPA) in the detection of uniparental disomy in these syndromes. The patient samples with regions of loss of heterozygosity (LOH), covering 15q11.2 and 11p15.5 critical loci, were analyzed with MS-MLPA to demonstrate the efficiency of SNP microarray in the detection of uniparental disomy (UPD). In a total of seven patients, LOH covering 15q11.2 and 11p15.5 critical loci was detected. Two (28.6%) of these seven patients showed aberrant methylation (suggesting UPD) in MS-MLPA. SNP microarray is a useful tool in the detection of LOH; however, it should be used with caution, since false-positive or false-negative LOH results can be obtained. Although methylation analysis is recommended as the first tier test in the diagnosis of most of the imprinting disorders, combining methylation analysis with SNP microarray can enhance our evaluation process.

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