scholarly journals Preferentially Paternal Origin of De Novo 11p13 Chromosome Deletions Revealed in Patients with Congenital Aniridia and WAGR Syndrome

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 812
Author(s):  
Tatyana A. Vasilyeva ◽  
Andrey V. Marakhonov ◽  
Natella V. Sukhanova ◽  
Sergey I. Kutsev ◽  
Rena A. Zinchenko
Keyword(s):  
De Novo ◽  
Chromosome Rearrangements ◽  
Paternal Allele ◽  
Large Chromosome ◽  
Pax6 Gene ◽  
Paternal Origin ◽  
Wagr Syndrome ◽  
Chromosome Breaks ◽  
Congenital Aniridia ◽  
Chromosome Deletions

The frequency of pathogenic large chromosome rearrangements detected in patients with different Mendelian diseases is truly diverse and can be remarkably high. Chromosome breaks could arise through different known mechanisms. Congenital PAX6-associated aniridia is a hereditary eye disorder caused by mutations or chromosome rearrangements involving the PAX6 gene. In our recent study, we identified 11p13 chromosome deletions in 30 out of 91 probands with congenital aniridia or WAGR syndrome (characterized by Wilms’ tumor, Aniridia, and Genitourinary abnormalities as well as mental Retardation). The loss of heterozygosity analysis (LOH) was performed in 10 families with de novo chromosome deletion in proband. In 7 out of 8 informative families, the analysis revealed that deletions occurred at the paternal allele. If paternal origin is not random, chromosome breaks could arise either (i) during spermiogenesis, which is possible due to specific male chromatin epigenetic program and its vulnerability to the breakage-causing factors, or (ii) in early zygotes at a time when chromosomes transmitted from different parents still carry epigenetic marks of the origin, which is also possible due to diverse and asymmetric epigenetic reprogramming occurring in male and female pronuclei. Some new data is needed to make a well-considered conclusion on the reasons for preferential paternal origin of 11p13 deletions.

scholarly journals A sporadic case of congenital aniridia caused by pericentric inversion inv(11)(p13q14) associated with a 977 kb deletion in the 11p13 region

2020 ◽  
Vol 13 (S8) ◽  
Author(s):  
Tatyana A. Vasilyeva ◽  
Andrey V. Marakhonov ◽  
Marina E. Minzhenkova ◽  
Zhanna G. Markova ◽  
Nika V. Petrova ◽  
...  
Keyword(s):  
General Population ◽  
Pericentric Inversion ◽  
De Novo ◽  
Wilms Tumor ◽  
Normal Karyotype ◽  
Paternal Allele ◽  
De Novo Mutations ◽  
Chromosome 11 ◽  
Dna Diagnosis ◽  
Congenital Aniridia

Abstract Background Because of the significant occurrence of “WAGR-region” deletions among de novo mutations detected in congenital aniridia, DNA diagnosis is critical for all sporadic cases of aniridia due to its help in making an early diagnosis of WAGR syndrome. Standard cytogenetic karyotype study is a necessary step of molecular diagnostics in patients with deletions and in the patients’ parents as it reveals complex chromosomal rearrangements and the risk of having another affected child, as well as to provide prenatal and/or preimplantation diagnostics. Case presentation DNA samples were obtained from the proband (a 2-year-old boy) and his two healthy parents. Molecular analysis revealed a 977.065 kb deletion that removed loci of the ELP4, PAX6, and RCN1 genes but did not affect the coding sequence of the WT1 gene. The deletion occurred de novo on the paternal allele. The patient had normal karyotype 46,XY and a de novo pericentric inversion of chromosome 11, inv(11)(p13q14). Conclusions We confirmed the diagnosis of congenital aniridia at the molecular level. For the patient, the risk of developing Wilms’ tumor is similar to that in the general population. The recurrence risk for sibs in the family is low, but considering the possibility of gonadal mosaicism, it is higher than in the general population.

scholarly journals Auxology Is a Valuable Instrument for the Clinical Diagnosis of SHOX Haploinsufficiency in School-Age Children with Unexplained Short Stature

2003 ◽  
Vol 88 (10) ◽  
pp. 4891-4896 ◽  
Author(s):  
Gerhard Binder ◽  
Michael B. Ranke ◽  
David D. Martin
Keyword(s):  
Short Stature ◽  
De Novo ◽  
Fragment Size ◽  
Mutation Screening ◽  
Idiopathic Short Stature ◽  
Paternal Allele ◽  
Leg Length ◽  
Sitting Height ◽  
Arm Span ◽  
Hand Radiography

Abstract SHOX (short stature homeobox-containing gene) mutations causing haploinsufficiency have been reported in some individuals with idiopathic short stature and in many patients with Leri-Weill-dyschondrosteosis. Around 80% of SHOX mutations are complete gene deletions, whereas diverse point mutations account for the rest. The aim of this study was to estimate the prevalence of SHOX mutations in children with idiopathic short stature and to give an unbiased characterization of the haploinsufficiency phenotype of such children. We recruited 140 children (61 girls), in our clinic, with idiopathic short stature, which was defined by the presence of normal IGF-I and free T4; a normal karyotype in females; the absence of endomysium antibodies, of chronic organic, psychological, or syndromatic disease; and by the lack of clear signs of any osteodysplasia. Height, arm span, and sitting height were recorded, and subischial leg length was calculated. Two highly polymorphic microsatellite markers located around the SHOX coding region (CA-SHOX repeat and DXYS233) were PCR-amplified with fluorescent primers and separated in an automatic sequencing machine. Analysis of parental DNA was performed in the probands who had only one fragment size of each of both markers. SHOX haploinsufficiency caused by a SHOX deletion was confirmed in three probands (2%), all females, who carried a de novo deletion through loss of the paternal allele. Their auxological data revealed a significant shortening of arms and legs in the presence of a low-normal sitting height, when compared with the other 137 children tested. Therefore, the extremities-trunk ratio (sum of leg length and arm span, divided by sitting height) for total height was significantly lower in the three SHOX haploinsufficient probands, in comparison with the whole group. This observation was confirmed with the auxological data of five additional patients (four females) previously diagnosed with SHOX haploinsufficiency; all but the youngest girl had height-adjusted extremities-trunk ratios more than 1 sd below the mean. All children with SHOX haploinsufficiency exhibited at least one characteristic radiological sign of Leri-Weill-dyschondrosteosis in their left-hand radiography, namely triangularization of the distal radial epiphysis, pyramidalization of the distal carpal row, or lucency of the distal ulnar border of the radius. Our observations suggest that it is rational to limit SHOX mutation screening to children with an extremities-trunk ratio less than 1.95 + 1/2 height (m) and to add a critical judgment of the hand radiography.

scholarly journals Allelic H3K27me3 to allelic DNA methylation switch maintains noncanonical imprinting in extraembryonic cells

2019 ◽  
Vol 5 (12) ◽  
pp. eaay7246 ◽  
Author(s):  
Zhiyuan Chen ◽  
Qiangzong Yin ◽  
Azusa Inoue ◽  
Chunxia Zhang ◽  
Yi Zhang
Keyword(s):  
Dna Methylation ◽  
De Novo ◽  
Genetic Manipulation ◽  
Paternal Allele ◽  
Gene Promoters ◽  
Maternal Allele ◽  
Mammalian Development ◽  
Placental Development ◽  
Early Embryos ◽  
Allele Specific

Faithful maintenance of genomic imprinting is essential for mammalian development. While germline DNA methylation–dependent (canonical) imprinting is relatively stable during development, the recently found oocyte-derived H3K27me3-mediated noncanonical imprinting is mostly transient in early embryos, with some genes important for placental development maintaining imprinted expression in the extraembryonic lineage. How these noncanonical imprinted genes maintain their extraembryonic-specific imprinting is unknown. Here, we report that maintenance of noncanonical imprinting requires maternal allele–specific de novo DNA methylation [i.e., somatic differentially methylated regions (DMRs)] at implantation. The somatic DMRs are located at the gene promoters, with paternal allele–specific H3K4me3 established during preimplantation development. Genetic manipulation revealed that both maternal EED and zygotic DNMT3A/3B are required for establishing somatic DMRs and maintaining noncanonical imprinting. Thus, our study not only reveals the mechanism underlying noncanonical imprinting maintenance but also sheds light on how histone modifications in oocytes may shape somatic DMRs in postimplantation embryos.

Prenatal diagnosis of a fetus with two balanced de novo chromosome rearrangements

1996 ◽  
Vol 66 (2) ◽  
pp. 197-199 ◽  
Author(s):  
Philip D. Cotter ◽  
Michele Caggana ◽  
Judith P. Willner ◽  
Arvind Babu ◽  
Robert J. Desnick
Keyword(s):  
Prenatal Diagnosis ◽  
De Novo ◽  
Chromosome Rearrangements

Parental origin of de novo chromosome rearrangements

1980 ◽  
Vol 53 (3) ◽  
pp. 343-347 ◽  
Author(s):  
J. Chamberlin ◽  
R. E. Magenis
Keyword(s):  
De Novo ◽  
Chromosome Rearrangements ◽  
Parental Origin

Complex Chromosomal Rearrangements

2018 ◽  
Author(s):  
R. J McKinlay Gardner ◽  
David J Amor
Keyword(s):  
De Novo ◽  
Chromosomal Rearrangements ◽  
Chromosome Rearrangements ◽  
Type I ◽  
Complex Type ◽  
Reproductive Risk ◽  
Clinically Normal ◽  
Complex Chromosomal Rearrangements ◽  
Very High ◽  
Complex Chromosome

Complex chromosome rearrangements (CCRs) include most of the rearrangements that would not be accounted for as “straightforward” classical categories. They may be translocations with three or more segments involved; or they may comprise a mix of translocation and, for example, inversion. Some can be extraordinarily complex. CCRs are classified as types I–IV, most falling into the “least complex” type I category, while types II–IV are grouped as “exceptional CCRs.” Many unbalanced CCRs have arisen de novo and imply no increased reproductive risk. The identification of the clinically normal balanced CCR carrier is less frequent, and for these people, the reproductive risks can be very high.

scholarly journals Thalassaemia intermedia caused by coinheritance of a β‐thalassaemia mutation and a de novo duplication of α‐globin genes in the paternal allele

2019 ◽  
Vol 186 (4) ◽  
pp. 620-624 ◽  
Author(s):  
Dejian Pang ◽  
Xuan Shang ◽  
Decheng Cai ◽  
Fei Zhu ◽  
Yi Cheng ◽  
...  
Keyword(s):  
De Novo ◽  
Paternal Allele ◽  
Globin Genes ◽  
Thalassaemia Intermedia

Identification of de novo deletions at the NF1 gene: no preferential paternal origin and phenotypic analysis of patients

1997 ◽  
Vol 99 (6) ◽  
pp. 720-726 ◽  
Author(s):  
M. Carmen Valero ◽  
Ignacio Pascual-Castroviejo ◽  
E. Velasco ◽  
Felipe Moreno ◽  
Concepción Hernández-Chico
Keyword(s):  
De Novo ◽  
Phenotypic Analysis ◽  
Paternal Origin ◽  
Nf1 Gene

scholarly journals Novel variants in PAX6 gene caused congenital aniridia in two Chinese families

Eye ◽  
2017 ◽  
Vol 31 (6) ◽  
pp. 956-961 ◽  
Author(s):  
R Zhang ◽  
S Linpeng ◽  
X Wei ◽  
H Li ◽  
Y Huang ◽  
...  
Keyword(s):  
Pax6 Gene ◽  
Chinese Families ◽  
Novel Variants ◽  
Congenital Aniridia

scholarly journals De novo paternal origin duplication of chromosome 11p15.5: report of two Chinese cases with Beckwith-Wiedemann syndrome

2017 ◽  
Vol 10 (1) ◽  
Author(s):  
Qin Wang ◽  
Qian Geng ◽  
Qinghua Zhou ◽  
Fuwei Luo ◽  
Peining Li ◽  
...  
Keyword(s):  
De Novo ◽  
Paternal Origin ◽  
Chromosome 11P15.5
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