scholarly journals Maternal uniparental disomy of chromosome 1

2020 ◽  
Author(s):  
Keyword(s):  
Uniparental Disomy ◽  
Chromosome 1 ◽  
Maternal Uniparental Disomy

scholarly journals Maternal Uniparental Disomy of Chromosome 1 with No Apparent Phenotypic Effects

1998 ◽  
Vol 63 (4) ◽  
pp. 1216-1220 ◽  
Author(s):  
L. Leigh Field ◽  
Rose Tobias ◽  
Wendy P. Robinson ◽  
Richard Paisey ◽  
Stephen Bain
Keyword(s):  
Uniparental Disomy ◽  
Chromosome 1 ◽  
Maternal Uniparental Disomy

Transfusion-Dependent Alpha-Spectrin Deficient Hemolytic Anemia Due to Maternal Uniparental Disomy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1030-1030
Author(s):  
Hannah Bogardus ◽  
Vincent P Schulz ◽  
Yelena Maksimova ◽  
Barbara A Miller ◽  
Bernard G. Forget ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Nonsense Mutation ◽  
Genomic Dna ◽  
Gene Locus ◽  
Uniparental Disomy ◽  
Chromosome 1 ◽  
Single Chromosome ◽  
Maternal Uniparental Disomy ◽  
Alpha Spectrin ◽  
Exon 19

Abstract Abstract 1030 We studied a girl with hereditary spherocytosis who required in utero transfusions and remained transfusion-dependent after birth. Initial clinical, laboratory, and biochemical characteristics of this patient have been described (Blood 78:3043, 1991). Severe alpha-spectrin deficiency was observed in membranes prepared from her marrow-derived cultured erythroid cells. Since this report, despite splenectomy at age 2 years, the proband remains transfusion-dependent. Our goal was to determine the molecular basis of the patient's transfusion-dependent anemia. Typically, alpha-spectrin deficiency is recessively inherited due to homozygous or compound heterozygous inactivating mutations of the alpha-spectrin gene. Genomic DNA from the proband was amplified using primers flanking the 52 coding exons and promoter region of the alpha-spectrin gene. Capillary electrophoresis-based nucleotide sequencing identified a homozygous nonsense mutation in exon 19 of the alpha-spectrin gene. The mother was heterozygous for this mutation; the father did not carry the mutation. To determine if a deletion involving the alpha-spectrin gene locus leading to homozygosity of the nonsense mutation in the proband was present, array comparative genomic hybridization (aCGH) was performed using the 44K CGH microarray (G4426A; Agilent Technologies, Santa Clara, CA). This array includes 44,000 60-mer oligonucleotides covering the entire human genome at a density of ∼14–15 oligonucleotides/MB. No deletions or rearrangements were identified by aCGH. To interrogate the alpha-spectrin locus at higher resolution, SNP typing of proband and parental genomic DNA was performed using the Illumina HumanHap 550 BeadChip. This array contains >550,000 SNPs and includes twenty intragenic SNPs in the alpha-spectrin gene locus. These studies identified a large region of homozygosity at 1q21, approximately 10 megabases in length, extending from rs6657293 (154,995,473, hg18) to rs6670426 (165,730,530) including the PRCC gene (155,003,897) to the CD247 gene (165,888,000) on chromosome 1q in genomic DNA from the proband. This region of homozygosity includes the alpha-spectrin gene locus and 158 other genes. Analyses of the SNP data also confirmed paternity and maternity, with a P-P-C heritability of 0.9997 and no inheritance violations in the alpha-spectrin gene region. Finally, to exclude the possibility of an intragenic microdeletion in the alpha-spectrin gene locus, copy number profiling using quantitative, real-time PCR was performed. Amplicons included exon 19, the location of the nonsense mutation, as well as exons 2, 17, 40, 52 and the 3'UTR. The proband and both parents had 2 copies of the corresponding alpha-spectrin region at all sites examined. No deletions were identified, excluding the possibility that a small deletion of the SPTA1 gene is the cause of homozygosity of exon 19 in the proband. Together, these data indicate there is partial maternal uniparental disomy of chromosome 1 in the proband and that reduction to homozygosity of the 1q region containing the maternal SPTA nonsense mutation is responsible for the alpha-spectrin deficient hemolytic anemia phenotype. This is the first case of uniparental disomy leading to an erythrocyte membrane-associated hemolytic anemia. The homozygosity associated with uniparental disomy consists of duplicated copies of alleles from a single chromosome, leading to increased risk of homozygosity for deleterious recessive mutations. Uniparental disomy should be considered when unexpected results are obtained during carrier testing in a recessive disorder. Disclosures: No relevant conflicts of interest to declare.

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.

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

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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