Prenatal diagnosis of complete maternal uniparental isodisomy of chromosome 4 in a fetus without congenital abnormality or inherited disease-associated variations

Hemophilia is an X-linked recessive bleeding disorder. In pregnant women carrier of hemophilia, the fetal sex can be determined by non-invasive analysis of fetal DNA circulating in the maternal blood. However, in case of a male fetus, conventional invasive procedures are required for the diagnosis of hemophilia. Fetal cells, circulating in the maternal bloodstream, are an ideal target for a safe non-invasive prenatal diagnosis. Nevertheless, the small number of cells and the lack of specific fetal markers have been the most limiting factors for their isolation. We aimed to develop monoclonal antibodies (mAbs) against the ribosomal protein RPS4Y1 expressed in male cells. By Western blotting, immunoprecipitation and immunofluorescence analyses performed on cell lysates from male human hepatoma (HepG2) and female human embryonic kidney (HEK293) we developed and characterized a specific monoclonal antibody against the native form of the male RPS4Y1 protein that can distinguish male from female cells. The availability of the RPS4Y1-targeting monoclonal antibody should facilitate the development of novel methods for the reliable isolation of male fetal cells from the maternal blood and their future use for non-invasive prenatal diagnosis of X-linked inherited disease such as hemophilia.

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LRBA Deficiency in a Patient With a Novel Homozygous Mutation Due to Chromosome 4 Segmental Uniparental Isodisomy

Frontiers in Immunology ◽

10.3389/fimmu.2018.02397 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 10

Author(s):

Pere Soler-Palacín ◽

Marina Garcia-Prat ◽

Andrea Martín-Nalda ◽

Clara Franco-Jarava ◽

Jacques G. Rivière ◽

...

Keyword(s):

Homozygous Mutation ◽

Chromosome 4 ◽

Uniparental Isodisomy ◽

Lrba Deficiency

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Congenital afibrinogenaemia caused by uniparental isodisomy of chromosome 4 containing a novel 15-kb deletion involving fibrinogen Aα-chain gene

European Journal of Human Genetics ◽

10.1038/sj.ejhg.5201207 ◽

2004 ◽

Vol 12 (11) ◽

pp. 891-898 ◽

Cited By ~ 24

Author(s):

Silvia Spena ◽

Stefano Duga ◽

Rosanna Asselta ◽

Flora Peyvandi ◽

Chularatana Mahasandana ◽

...

Keyword(s):

Chain Gene ◽

Chromosome 4 ◽

Uniparental Isodisomy

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Prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from ring chromosome 4

Taiwanese Journal of Obstetrics and Gynecology ◽

10.1016/j.tjog.2011.04.002 ◽

2011 ◽

Vol 50 (2) ◽

pp. 188-195 ◽

Cited By ~ 7

Author(s):

Chih-Ping Chen ◽

Ming Chen ◽

Yi-Ning Su ◽

Fuu-Jen Tsai ◽

Schu-Rern Chern ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Marker Chromosome ◽

Ring Chromosome ◽

Chromosome 4 ◽

Molecular Cytogenetic ◽

Small Supernumerary Marker Chromosome ◽

Cytogenetic Characterization

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Prenatal Diagnosis of Complete Paternal Uniparental Isodisomy for Chromosome 3: A Case Report

10.21203/rs.3.rs-778220/v1 ◽

2021 ◽

Author(s):

xiufen bu ◽

Xu Li ◽

Shihao Zhou ◽

Liangcheng Shi ◽

Xuanyu Jiang ◽

...

Keyword(s):

Genetic Counseling ◽

Prenatal Diagnosis ◽

Snp Array ◽

Uniparental Disomy ◽

Rare Condition ◽

Normal Karyotype ◽

Chromosome 3 ◽

Uniparental Isodisomy ◽

Normal Ultrasound ◽

Physical Findings

Abstract Background Paternal uniparental disomy (UPD) of chromosome 3 is a very rare condition. At present, only 5 cases of paternal UPD(3) has been reported. This was the second ascertained paternal UPD(3) with no apparent disease phenotype.Case presentation We hereby reported a case of a fetus with normal karyotype and normal ultrasound features at the whole gestation. A copy neutral regions of homozygosity on chromosome 3 was indentified by Single Nucleotide Polymophism array (SNP array). Subsequent SNP array data of parent–child trios showed the fetus has carried complete paternal uniparental isodisomy (isoUPD) of chromosome 3. The parents decided to continue the pregnancy after genetic counseling. The neonate had normal physical findings at birth and develops normally after 1.5 years. Conclusions The findings could provide further evidence to confirm that there was no important imprinted genes causing serious diseases on paternal chromosome 3 and provided a reference for the prenatal diagnosis and genetic counseling of UPD(3) in the future.

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Partial trisomy 4q and monosomy 5p inherited from a maternal translocationt(4;5)(q33;p15) in three adverse pregnancies

10.21203/rs.3.rs-17019/v2 ◽

2020 ◽

Author(s):

Jingbo Zhang ◽

Bei Zhang ◽

Tong Liu ◽

Huihui Xie ◽

Jingfang Zhai

Keyword(s):

Prenatal Diagnosis ◽

Chromosomal Abnormalities ◽

Genetic Diagnosis ◽

Partial Trisomy ◽

Distal Region ◽

Chromosome 17 ◽

Chromosome 1 ◽

Chromosome 4 ◽

Chromosome 5 ◽

Balanced Translocation

Abstract Background: Carriers of balanced reciprocal chromosomal translocations are at known reproductive risk for offspring with unbalanced genotypes and resultantly abnormal phenotypes. Once fertilization of a balanced translocation gamete with a normal gamete, the partial monomer or partial trisomy embryo will undergo abortion, fetal arrest or fetal malformations. We reported a woman with chromosomal balanced translocation who had two adverse pregnancies. Prenatal diagnosis was made for her third pregnancy to provide genetic counseling and guide her fertility. Case presentation: We presented a woman with chromosomal balanced translocation who had three adverse pregnancies. Routine G banding and CNV-seq were used to analyze the chromosome karyotypes and copy number variants of amniotic fluid cells and peripheral blood. The karyotype of the woman was 46,XX,t(4;5)(q33;p15). During her first pregnancy, odinopoeia was performed due to fetal edema and abdominal fluid. The umbilical cord tissue of the fetus was examined by CNV-seq. The results showed a genomic gain of 24.18 Mb at 4q32.3-q35.2 and a genomic deletion of 10.84 Mb at 5p15.33-p15.2 and 2.36 Mb at 15q11.1-q11.2. During her second pregnancy, she did not receive a prenatal diagnosis because a routine prenatal ultrasound examination found no abnormalities. In 2016, she gave birth to a boy.. The karyotype the of the boy was 46,XY,der(5)t(4;5)(q33;p15)mat. The results of CNV-seq showed a deletion of short arm of chromosome 5 capturing regions 5p15.33p15.2, a copy gain of the distal region of chromosome 4 at segment 4q32.3q35.2, a duplication of chromosome 1 at segment 1q41q42.11 and a duplication of chromosome 17 at segment 17p12. During her third pregnancy, she underwent amniocentesis at 17 weeks of gestation. Chromosome karyotype hinted 46,XY,der(5)t(4;5)(q33;p15)mat. Results of CNV-seq showed a deletion of short arm (p) of chromosome 5 at the segment 5p15.33p15.2 and a duplication of the distal region of chromosome 4 at segment 4q32.3q35.2.Conclusions: Chromosomal abnormalities in three pregnancies were inherited from the mother. Preimplantation genetic diagnosis is recommended to prevent the birth of children with chromosomal abnormalities.

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Genetic analysis of 62 Chinese families with Duchenne muscular dystrophy and strategies of prenatal diagnosis in a single center

BMC Medical Genetics ◽

10.1186/s12881-019-0912-x ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Jingjing Zhang ◽

Dingyuan Ma ◽

Gang Liu ◽

Yuguo Wang ◽

An Liu ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

De Novo ◽

Clinical Symptoms ◽

Perinatal Care ◽

Genetic Diagnosis ◽

Point Mutations ◽

Inherited Disease ◽

Positive Results

Abstract Background Duchenne muscular dystrophy (DMD) is a severe X-linked recessive neuromuscular disorder. Patients with DMD usually have severe and fatal symptoms, including progressive irreversible muscle weakness and atrophy complicated with gastrocnemius muscle pseudohypertrophy. DMD is caused by mutations in the dystrophin-encoding DMD gene, including large rearrangements and point mutations. This retrospective study was aimed at supplying information on our 4-year clinical experience of DMD genetic and prenatal diagnosis at the Department of Prenatal Diagnosis in Women’s Hospital of Nanjing Medical University. Methods Multiplex ligation-dependent probe amplification (MLPA) was used to detect the exon deletions or duplications. And Ion AmpliSeq™ panel for inherited disease was used as the next-generation sequencing (NGS) method to identify the point mutations in exons of DMD gene, but the introns were not sequenced. Results In this study, the large deletions and duplications of DMD gene were detected in 32 (51.6%) of the 62 families, while point mutations were detected in 20 families (32.3%). The remaining 10 families with a negative genetic diagnosis need to be reevaluated for clinical symptoms or be detected by other molecular methods. Notably, six novel mutations were identified, including c.412A > T(p.Lys138*), c.2962delT(p.Ser988Leufs*16), c.6850dupA (p.Ser2284Lysfs*7), c.5139dupA (p.Glu 1714Argfs*5), c.6201_6203delGCCins CCCA(p.Val2069Cysfs*14) and c.10705A > T (p.Lys3569*). In 52 families with positive results, 45 mothers (86.5%) showed positive results during carrier testing and de novo mutations arose in 7 probands. The prenatal diagnosis was offered to 34 fetuses whether the pregnant mother was a carrier or not. As a result, eight male fetuses were affected, three female fetuses were carriers, and the remaining fetuses had no pathogenic mutation. Conclusions This study reported that MLPA and NGS could be used for screening the DMD gene mutations. Furthermore, the stepwise procedure of prenatal diagnosis of DMD gene was shown in our study, which is important for assessing the mutation type of fetuses and providing perinatal care in DMD high-risk families.

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