scholarly journals Maternal uniparental disomy of chromosome 4

2020 ◽  
Author(s):  
Keyword(s):  
Uniparental Disomy ◽  
Chromosome 4 ◽  
Maternal Uniparental Disomy

Maternal uniparental disomy of chromosome 4 and homozygous novel mutation in the WFS1 gene in a paediatric patient with Wolfram syndrome

2015 ◽  
Vol 41 (5) ◽  
pp. 433-435 ◽  
Author(s):  
D.T. Papadimitriou ◽  
E. Manolakos ◽  
C. Bothou ◽  
G. Zoupanos ◽  
I. Papoulidis ◽  
...  
Keyword(s):  
Paediatric Patient ◽  
Novel Mutation ◽  
Uniparental Disomy ◽  
Wolfram Syndrome ◽  
Chromosome 4 ◽  
Maternal Uniparental Disomy ◽  
Wfs1 Gene

Maternal chromosome 4 heterodisomy/isodisomy and Bβ chain Trp323X mutation resulting in severe hypodysfibrinogenaemia

2012 ◽  
Vol 108 (10) ◽  
pp. 654-661 ◽  
Author(s):  
Xiaodong Xi ◽  
Qiulan Ding ◽  
Qi Ouyang ◽  
Xuefeng Wang ◽  
Yiping Shen ◽  
...  
Keyword(s):  
Rare Case ◽  
Uniparental Disomy ◽  
Clinical History ◽  
Chromosome 4 ◽  
Microsatellite Genotyping ◽  
Array Analysis ◽  
Genotyping Array ◽  
Maternal Uniparental Disomy ◽  
Mixed Nature ◽  
Meiosis I

SummaryWe report a rare case of congenital hypodysfibrinogenaemia due to maternal uniparental disomy of chromosome 4 (mat UPD 4) and a maternally inherited novel nonsense mutation Trp323X in the fibrinogen Bβ chain (FGB) gene. Western blot analysis of patient's plasma revealed an abnormal fibrinogen which consisted of truncated Bβ chain and normal Aα and γ chains. Patient's clinical history and laboratory evidence are presented. Microsatellite genotyping analysis revealed a mixed nature of heterodisomy and isodisomy along chromosome 4. High density SNP genotyping array analysis further confirmed the mat UPD 4 and defined two segments of chromosome 4 (4pter-p15.33 and 4q31.21–4q32.3) as maternal isodisomy (iUPD4) and the remaining regions as maternal heterodisomy (hUPD4), with the FGB gene carrying the mutation resided in the iUPD4 region on the long (q) arm. It was predicted that the segmental nature of iUPD and hUPD was caused by three recombination events at positions around 167.96 cM, 145.51 cM and 14.40 cM on chromosome 4 followed by a meiosis I non-disjunction. This case is clinically and molecularly unique and offers an opportunity for understanding novel mechanisms of congenital hypodysfibrinogenaemia associated with complex UPD and fibrinogen secretion.

Two cases of confined placental mosaicism for chromosome 4, including one with maternal uniparental disomy

2001 ◽  
Vol 21 (1) ◽  
pp. 36-39 ◽  
Author(s):  
B. D. Kuchinka ◽  
I. J. Barrett ◽  
G. Moya ◽  
J. M. S�nchez ◽  
S. Langlois ◽  
...  
Keyword(s):  
Uniparental Disomy ◽  
Chromosome 4 ◽  
Maternal Uniparental Disomy ◽  
Placental Mosaicism

scholarly journals One test for all: whole exome sequencing significantly improves the diagnostic yield in growth retarded patients referred for molecular testing for Silver–Russell syndrome

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Robert Meyer ◽  
Matthias Begemann ◽  
Christian Thomas Hübner ◽  
Daniela Dey ◽  
Alma Kuechler ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Diagnostic Yield ◽  
Uniparental Disomy ◽  
Molecular Testing ◽  
Main Body ◽  
Comprehensive Overview ◽  
Maternal Uniparental Disomy ◽  
Whole Exome ◽  
Silver Russell Syndrome

Abstract Background Silver-Russell syndrome (SRS) is an imprinting disorder which is characterised by severe primordial growth retardation, relative macrocephaly and a typical facial gestalt. The clinical heterogeneity of SRS is reflected by a broad spectrum of molecular changes with hypomethylation in 11p15 and maternal uniparental disomy of chromosome 7 (upd(7)mat) as the most frequent findings. Monogenetic causes are rare, but a clinical overlap with numerous other disorders has been reported. However, a comprehensive overview on the contribution of mutations in differential diagnostic genes to phenotypes reminiscent to SRS is missing due to the lack of appropriate tests. With the implementation of next generation sequencing (NGS) tools this limitation can now be circumvented. Main body We analysed 75 patients referred for molecular testing for SRS by a NGS-based multigene panel, whole exome sequencing (WES), and trio-based WES. In 21/75 patients a disease-causing variant could be identified among them variants in known SRS genes (IGF2, PLAG1, HMGA2). Several patients carried variants in genes which have not yet been considered as differential diagnoses of SRS. Conclusions WES approaches significantly increase the diagnostic yield in patients referred for SRS testing. Several of the identified monogenetic disorders have a major impact on clinical management and genetic counseling.

scholarly journals Maternal Uniparental Disomy of Chromosome 20 (UPD(20)mat) as Differential Diagnosis of Silver Russell Syndrome: Identification of Three New Cases

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 588
Author(s):  
Pierpaola Tannorella ◽  
Daniele Minervino ◽  
Sara Guzzetti ◽  
Alessandro Vimercati ◽  
Luciano Calzari ◽  
...  
Keyword(s):  
Growth Retardation ◽  
Molecular Mechanisms ◽  
Uniparental Disomy ◽  
Postnatal Growth ◽  
Molecular Diagnostic ◽  
Growth Delay ◽  
Molecular Defect ◽  
Maternal Uniparental Disomy ◽  
Feeding Difficulties ◽  
Silver Russell Syndrome

Silver Russell Syndrome (SRS, MIM #180860) is a rare growth retardation disorder in which clinical diagnosis is based on six features: pre- and postnatal growth failure, relative macrocephaly, prominent forehead, body asymmetry, and feeding difficulties (Netchine–Harbison clinical scoring system (NH-CSS)). The molecular mechanisms consist in (epi)genetic deregulations at multiple loci: the loss of methylation (LOM) at the paternal H19/IGF2:IG-DMR (chr11p15.5) (50%) and the maternal uniparental disomy of chromosome 7 (UPD(7)mat) (10%) are the most frequent causes. Thus far, about 40% of SRS remains undiagnosed, pointing to the need to define the rare mechanisms in such a consistent fraction of unsolved patients. Within a cohort of 176 SRS with an NH-CSS ≥ 3, a molecular diagnosis was disclosed in about 45%. Among the remaining patients, we identified in 3 probands (1.7%) with UPD(20)mat (Mulchandani–Bhoj–Conlin syndrome, OMIM #617352), a molecular mechanism deregulating the GNAS locus and described in 21 cases, characterized by severe feeding difficulties associated with failure to thrive, preterm birth, and intrauterine/postnatal growth retardation. Our patients share prominent forehead, feeding difficulties, postnatal growth delay, and advanced maternal age. Their clinical assessment and molecular diagnostic flowchart contribute to better define the characteristics of this rare imprinting disorder and to rank UPD(20)mat as the fourth most common pathogenic molecular defect causative of SRS.

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