scholarly journals De novo splice site variant of ARID1B associated with pathogenesis of Coffin–Siris syndrome

2019 ◽  
Vol 7 (12) ◽  
Author(s):  
Laura Pranckėnienė ◽  
Evelina Siavrienė ◽  
Lucie Gueneau ◽  
Eglė Preikšaitienė ◽  
Violeta Mikštienė ◽  
...  
Keyword(s):  
Splice Site ◽  
De Novo ◽  
Splice Site Variant

scholarly journals A case of de novo splice site variant inSLC35A2showing developmental delays, spastic paraplegia, and delayed myelination

2019 ◽  
Vol 7 (8) ◽  
Author(s):  
Sachiko Miyamoto ◽  
Mitsuko Nakashima ◽  
Tsukasa Ohashi ◽  
Takuya Hiraide ◽  
Kenji Kurosawa ◽  
...  
Keyword(s):  
Splice Site ◽  
Developmental Delays ◽  
De Novo ◽  
Spastic Paraplegia ◽  
Splice Site Variant ◽  
Delayed Myelination

scholarly journals P.123 Severe DNM1 Encephalopathy with Dysmyelination due to Recurrent Splice Site Pathogenic Variant

2021 ◽  
Vol 48 (s3) ◽  
pp. S54-S54
Author(s):  
AN Sahly ◽  
E Krochmalnek ◽  
J St-Onge ◽  
M Srour ◽  
KA Myers
Keyword(s):  
Splice Site ◽  
De Novo ◽  
Subcortical White Matter ◽  
Pathogenic Variant ◽  
Pcr Analysis ◽  
Global Developmental Delay ◽  
Missense Mutations ◽  
Central Domain ◽  
Splice Site Variant ◽  
T2 Hyperintensity

Background: Patients with DNM1-encephalopathy almost exclusively have missense variants, mostly in the GTPase domain of DNM1. Delayed myelination has been reported in at least three patients with DNM1-encephalopathy, all with missense mutations in the DNM1 central domain. Only one DNM1 splice-site variant has previously been reported, and the authors questioned whether the variant accounted for all aspects of the patient’s phenotype. Methods: Case-Report. Results: Our patient had hypotonia and brief multifocal tonic seizures from age-1-month. He still has profound global developmental delay, daily seizures and microcephaly. MRI-Brain at age-21-months showed T2 hyperintensity in the bilateral periventricular and subcortical white matter; spectroscopy showed a questionable lactate peak and an elevated choline peak relative to N-acetylaspartate. Clinical gene-panel identified a heterozygous de novo pathogenic variant in intron 9 of DNM1 (c.1197-8G > A; IVS9- 8G>A). In-silico tools categorized this variant as deleterious secondary to a splicing defect. RT-PCR analysis on peripheral blood was unsuccessful as DNM1 expression is extremely low outside of the brain. Conclusions: Our patient carried the same DNM1 variant previously reported, indicating this is a recurrent pathogenic splice-site variant. The spectroscopic abnormalities suggest a possible element of demyelination in DNM1 variants of the central domain, though the mechanism remains unclear.

scholarly journals Lethal chondrodysplasia in a family of Holstein cattle is associated with a de novo splice site variant of COL2A1

2016 ◽  
Vol 12 (1) ◽  
Author(s):  
Jørgen S. Agerholm ◽  
Fiona Menzi ◽  
Fintan J. McEvoy ◽  
Vidhya Jagannathan ◽  
Cord Drögemüller
Keyword(s):  
Splice Site ◽  
De Novo ◽  
Holstein Cattle ◽  
Splice Site Variant

scholarly journals A rare large duplication of MLH1 identified in Lynch syndrome

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Abhishek Kumar ◽  
Nagarajan Paramasivam ◽  
Obul Reddy Bandapalli ◽  
Matthias Schlesner ◽  
Tianhui Chen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Lynch Syndrome ◽  
Splice Site ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Splice Donor Site ◽  
Laboratory Diagnostics ◽  
Mmr Genes ◽  
Base Pair Deletion ◽  
Splice Site Variant

Abstract Background The most frequently identified strong cancer predisposition mutations for colorectal cancer (CRC) are those in the mismatch repair (MMR) genes in Lynch syndrome. Laboratory diagnostics include testing tumors for immunohistochemical staining (IHC) of the Lynch syndrome-associated DNA MMR proteins and/or for microsatellite instability (MSI) followed by sequencing or other techniques, such as denaturing high performance liquid chromatography (DHPLC), to identify the mutation. Methods In an ongoing project focusing on finding Mendelian cancer syndromes we applied whole-exome/whole-genome sequencing (WES/WGS) to 19 CRC families. Results Three families were identified with a pathogenic/likely pathogenic germline variant in a MMR gene that had previously tested negative in DHPLC gene variant screening. All families had a history of CRC in several family members across multiple generations. Tumor analysis showed loss of the MMR protein IHC staining corresponding to the mutated genes, as well as MSI. In family A, a structural variant, a duplication of exons 4 to 13, was identified in MLH1. The duplication was predicted to lead to a frameshift at amino acid 520 and a premature stop codon at amino acid 539. In family B, a 1 base pair deletion was found in MLH1, resulting in a frameshift and a stop codon at amino acid 491. In family C, we identified a splice site variant in MSH2, which was predicted to lead loss of a splice donor site. Conclusions We identified altogether three pathogenic/likely pathogenic variants in the MMR genes in three of the 19 sequenced families. The MLH1 variants, a duplication of exons 4 to 13 and a frameshift variant, were novel, based on the InSiGHT and ClinVar databases; the MSH2 splice site variant was reported by a single submitter in ClinVar. As a variant class, duplications have rarely been reported in the MMR gene literature, particularly those covering several exons.

A novel BTK gene mutation creates a de-novo splice site in an X-linked agammaglobulinemia patient

Gene ◽  
2015 ◽  
Vol 560 (2) ◽  
pp. 245-248 ◽  
Author(s):  
Chai Teng Chear ◽  
Adiratna Mat Ripen ◽  
Sharifah Adlena Syed Mohamed ◽  
Jasbir Singh Dhaliwal
Keyword(s):  
Gene Mutation ◽  
Splice Site ◽  
De Novo

scholarly journals A 5′ splice site mutation affecting the pre-mRNA splicing of two upstream exons in the collagen COL1A1 gene. Exon 8 skipping and altered definition of exon 7 generates truncated proα1(I) chains with a non-collagenous insertion destabilizing the triple helix

1994 ◽  
Vol 302 (3) ◽  
pp. 729-735 ◽  
Author(s):  
J F Bateman ◽  
D Chan ◽  
I Moeller ◽  
M Hannagan ◽  
W G Cole
Keyword(s):  
Splice Site ◽  
De Novo ◽  
Donor Site ◽  
Mrna Splicing ◽  
Splice Donor Site ◽  
Sequence Motif ◽  
Type I ◽  
Splice Donor ◽  
Site Mutation ◽  
Definition Of

A heterozygous de novo G to A point mutation in intron 8 at the +5 position of the splice donor site of the gene for the pro alpha 1(I) chain of type I procollagen, COL1A1, was defined in a patient with type IV osteogenesis imperfecta. The splice donor site mutation resulted not only in the skipping of the upstream exon 8 but also unexpectedly had the secondary effect of activating a cryptic splice site in the next upstream intron, intron 7, leading to re-definition of the 3′ limit of exon 7. These pre-mRNA splicing aberrations cause the deletion of exon 8 sequences from the mature mRNA and the inclusion of 96 bp of intron 7 sequence. Since the mis-splicing of the mutant allele product resulted in the maintenance of the correct codon reading frame, the resultant pro alpha 1(I) chain contained a short non-collagenous 32-amino-acid sequence insertion within the repetitive Gly-Xaa-Yaa collagen sequence motif. At the protein level, the mutant alpha 1(I) chain was revealed by digestion with pepsin, which cleaved the mutant procollagen within the protease-sensitive non-collagenous insertion, producing a truncated alpha 1(I). This protease sensitivity demonstrated the structural distortion to the helical structure caused by the insertion. In long-term culture with ascorbic acid, which stimulates the formation of a mature crosslinked collagen matrix, and in tissues, there was no evidence of the mutant chain, suggesting that during matrix formation the mutant chain was unable to stably incorporated into the matrix and was degraded proteolytically.

A common founder effect of the splice site variant c.-23 + 1G > A in GJB2 gene causing autosomal recessive deafness 1A (DFNB1A) in Eurasia

2021 ◽  
Author(s):  
Aisen V. Solovyev ◽  
Alena Kushniarevich ◽  
Elena Bliznetz ◽  
Marita Bady-Khoo ◽  
Maria R. Lalayants ◽  
...  
Keyword(s):  
Splice Site ◽  
Founder Effect ◽  
Autosomal Recessive ◽  
Gjb2 Gene ◽  
C 23 ◽  
Common Founder ◽  
Splice Site Variant

A de novo COL17A1 splice-site mutation causing a 7-bp deletion in a Taiwanese patient with junctional epidermolysis bullosa

2021 ◽  
Vol 31 (2) ◽  
pp. 267-269
Author(s):  
Ping-Chen Hou ◽  
Wei-Ting Tu ◽  
Peng-Chieh Chen ◽  
Bryan Edgar K. Guevara ◽  
Yu-Fen Yen ◽  
...  
Keyword(s):  
Splice Site ◽  
Epidermolysis Bullosa ◽  
De Novo ◽  
Splice Site Mutation ◽  
Site Mutation ◽  
Junctional Epidermolysis Bullosa ◽  
Taiwanese Patient

A splice-site variant in ANKRD11 associated with classical KBG syndrome

2017 ◽  
Vol 173 (10) ◽  
pp. 2844-2846 ◽  
Author(s):  
Karen J. Low ◽  
Alison Hills ◽  
Maggie Williams ◽  
Celia Duff-Farrier ◽  
Shane McKee ◽  
...  
Keyword(s):  
Splice Site ◽  
Kbg Syndrome ◽  
Splice Site Variant
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