Symptomatic mosaicism for a novel FBN1 splice site variant in a parent causing inherited neonatal Marfan syndrome

2021 ◽  
Author(s):  
Julianne K. Postma ◽  
Luis Altamirano‐Diaz ◽  
C. Anthony Rupar ◽  
Victoria M. Siu
Keyword(s):  
Marfan Syndrome ◽  
Splice Site ◽  
Neonatal Marfan Syndrome ◽  
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 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 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

scholarly journals A splice site variant in INPP5E causes diffuse cystic renal dysplasia and hepatic fibrosis in dogs

PLoS ONE ◽  
2018 ◽  
Vol 13 (9) ◽  
pp. e0204073 ◽  
Author(s):  
Kati J. Dillard ◽  
Marjo K. Hytönen ◽  
Daniel Fischer ◽  
Kimmo Tanhuanpää ◽  
Mari S. Lehti ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
Splice Site ◽  
Renal Dysplasia ◽  
Cystic Renal Dysplasia ◽  
Splice Site Variant

Cardiac Transplantation in Neonatal Marfan Syndrome - A Life-Saving Approach

2005 ◽  
Vol 53 ◽  
pp. S146-S148 ◽  
Author(s):  
T. Krasemann ◽  
S. Kotthoff ◽  
H.-G. Kehl ◽  
V. Debus ◽  
T. D. T. Tjan ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Cardiac Transplantation ◽  
Life Saving ◽  
Neonatal Marfan Syndrome

scholarly journals A Case of Neonatal Marfan Syndrome: A Management Conundrum and the Role of a Multidisciplinary Team

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Elliott J. Carande ◽  
Samuel J. Bilton ◽  
Satish Adwani
Keyword(s):  
Marfan Syndrome ◽  
Surgical Intervention ◽  
Rare Condition ◽  
Mitral Valve Regurgitation ◽  
Left Ventricular ◽  
Cardiac Complications ◽  
Chromosome 15 ◽  
Fibrillin 1 ◽  
Neonatal Marfan Syndrome

Neonatal Marfan syndrome (nMFS) is a rare condition with a poor prognosis. It is genotypically and phenotypically distinct from the typical Marfan syndrome and carries a poorer prognosis. This case report describes the progression of a 14-month-old girl diagnosed with nMFS at 5 months of age. Her diagnosis followed the identification of a fibrillin-1 mutation (FBN1gene, exon 26, chromosome 15), which is a common locus of nMFS. This patient developed severe cardiac complications resulting in congestive cardiac failure in early life and required major cardiac surgery. Since surgical intervention, our patient is still reliant on a degree of ventilator support, but the patient has gained weight and echocardiography has demonstrated improved left ventricular function and improved tricuspid and mitral valve regurgitation. Therefore, we argue the importance of a cautious multidisciplinary approach to early surgical intervention in cases of nMFS.

Fluoropyrimidine toxicity in patients with dihydropyrimidine dehydrogenase splice site variant: the need for further revision of dose and schedule

2013 ◽  
Vol 8 (5) ◽  
pp. 417-423 ◽  
Author(s):  
Elena Magnani ◽  
Enrico Farnetti ◽  
Davide Nicoli ◽  
Bruno Casali ◽  
Luisa Savoldi ◽  
...  
Keyword(s):  
Splice Site ◽  
Dihydropyrimidine Dehydrogenase ◽  
Splice Site Variant

Primary trabeculodysgenesis in association with neonatal Marfan syndrome

2004 ◽  
Vol 128A (4) ◽  
pp. 418-421 ◽  
Author(s):  
Charlotte M. Whitelaw ◽  
Samira Anwar ◽  
Lesley C. Adès ◽  
Glen A. Gole ◽  
James E. Elder ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Neonatal Marfan Syndrome

Neonatal Marfan syndrome with missense variant of c.3706T>C undergoing bilateral atrioventricular valve replacement

2021 ◽  
pp. 1-4
Author(s):  
Junpei Kawamura ◽  
Kentaro Ueno ◽  
Yoshifumi Kawano
Keyword(s):  
Marfan Syndrome ◽  
Valve Replacement ◽  
Tricuspid Valve ◽  
Rare Condition ◽  
Missense Variant ◽  
Tricuspid Valve Replacement ◽  
Genetic Syndrome ◽  
Fibrillin 1 ◽  
Valve Insufficiency ◽  
Neonatal Marfan Syndrome

Abstract Neonatal Marfan syndrome is a rare condition with poor prognosis because of severe mitral and/or tricuspid valve insufficiency. Mitral valve replacement is sometimes required in early infancy, while tricuspid valve replacement is rarely done. We report the first infant neonatal Marfan syndrome case with a missense variant of c.3706T>C in the fibrillin-1 gene that was successfully managed by mitral and tricuspid valve replacement. Early multiple-valve replacement may sometimes be required during infant age in this genetic syndrome.

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