scholarly journals MLH1 Exon 12 Gene Deletion Leading to Lynch Syndrome: A Case Report

2021 ◽  
pp. 1-7
Author(s):  
Shiyun Cui ◽  
Xiao Zhang ◽  
Ruihan Zou ◽  
Fan Ye ◽  
Yutong Wang ◽  
...  
Keyword(s):  
Case Report ◽  
Lynch Syndrome ◽  
Splice Site Mutation ◽  
Multiple Organ ◽  
Heterozygous Mutation ◽  
Site Mutation ◽  
Mlh1 Gene ◽  
Next Generation Sequencing Technology ◽  
Gene Testing ◽  
Tissue Specimens

<b><i>Introduction:</i></b> Deleterious heterozygous mutation of the MLH1 gene is an important cause of Lynch syndrome (LS), an autosomal dominant cancer caused by functional defects in the DNA mismatch repair (MMR) complex. <b><i>Case Report:</i></b> The proband was a 35-year-old patient with confirmed colorectal cancer (CRC). Immunohistochemical (IHC) staining revealed the absence of MLH1 and PMS2 expression in the colorectal tissue specimens of the patient. Genetic counselling and tumor gene testing were performed using next-generation sequencing technology. The genetic tumor verification report showed the deletion of 4 bases in exon 12 of the tested MLH1 gene and a transcoding mutation. To our knowledge, this germline splice site mutation of MLH1 has not been reported before. The proband accepted several therapeutic regimens including PD-1 inhibitor and ultimately died of multiple organ failure. <b><i>Conclusion:</i></b> Nonsense mutations and frameshift mutations of MMR genes are the most common causes of LS. Common mutations include those in MSH2, MLH1, MSH6, and PMS2. We report a mutation of MLH1 that has never been reported before. We recommend that patients with a history of colon or rectal cancer receive universal MMR or MSI testing and checkpoint inhibitor therapy for the first-line treatment of deficient MMR CRC.

Novel splice site mutation in the LIPH gene in a patient with autosomal recessive woolly hair/hypotrichosis: Case report and published work review

2018 ◽  
Vol 45 (5) ◽  
pp. 613-617 ◽  
Author(s):  
Yukari Mizukami ◽  
Ryota Hayashi ◽  
Daisuke Tsuruta ◽  
Yutaka Shimomura ◽  
Koji Sugawara
Keyword(s):  
Case Report ◽  
Splice Site ◽  
Autosomal Recessive ◽  
Splice Site Mutation ◽  
Site Mutation ◽  
Woolly Hair

scholarly journals Eleven percent intact PGM3 in a severely immunodeficient patient with a novel splice-site mutation, a case report

2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Karin E. Lundin ◽  
Qing Wang ◽  
Abdulrahman Hamasy ◽  
Per Marits ◽  
Mehmet Uzunel ◽  
...  
Keyword(s):  
Case Report ◽  
Splice Site ◽  
Splice Site Mutation ◽  
Site Mutation

scholarly journals Case report of a novel homozygous splice site mutation in PLA2G6 gene causing infantile neuroaxonal dystrophy in a Sudanese family

2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Liena E. O. Elsayed ◽  
Inaam N. Mohammed ◽  
Ahlam A. A. Hamed ◽  
Maha A. Elseed ◽  
Mustafa A. M. Salih ◽  
...  
Keyword(s):  
Case Report ◽  
Splice Site ◽  
Splice Site Mutation ◽  
Neuroaxonal Dystrophy ◽  
Site Mutation ◽  
Infantile Neuroaxonal Dystrophy

scholarly journals A novel splice site mutation in WAS gene in patient with Wiskott-Aldrich syndrome and chronic colitis: a case report

2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Hossein Esmaeilzadeh ◽  
Mohammad Reza Bordbar ◽  
Hassan Dastsooz ◽  
Mohammad Silawi ◽  
Mohammad Ali Farazi Fard ◽  
...  
Keyword(s):  
Case Report ◽  
Splice Site ◽  
Splice Site Mutation ◽  
Chronic Colitis ◽  
Site Mutation ◽  
Wiskott Aldrich Syndrome ◽  
Was Gene

scholarly journals A Novel Splice-Site Mutation in MSH2 Is Associated With the Development of Lynch Syndrome

2020 ◽  
Vol 10 ◽  
Author(s):  
Juyi Li ◽  
Yuanyuan Li ◽  
Haichun Ni ◽  
Zhibin Yang ◽  
Jian Chen ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Splice Site ◽  
Splice Site Mutation ◽  
Site Mutation

Overlooking MMR deficiency in carriers of certain pathogenic variants by routine MSI and/or IHC testing in Lynch syndrome: Implications for a wider MMR deficiency testing.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16107-e16107
Author(s):  
Marija Staninova Stojovska ◽  
Katerina Kubelka Sabit ◽  
Dzengis Jasar ◽  
Rubens Jovanovic ◽  
Nadica Matevska ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Positive Result ◽  
Splice Site Mutation ◽  
The Other ◽  
Sporadic Colorectal Cancer ◽  
Site Mutation ◽  
Potential Implication ◽  
Mmr Genes ◽  
Pathogenic Variants ◽  
Mmr Deficiency

e16107 Background: DNA mismatch repair (MMR) deficiency occurs in both inherited/sporadic colorectal cancer (CRC) and endometrial cancer, but it may also be found in some other types of cancer. At present, MMR status testing in clinical practice is recommended for all CRC patients in order to identify those who should be offered genetic testing for the Lynch syndrome (LS), inform disease prognosis, and guide therapeutic management.There are two commonly accepted methods for MMR deficiency analysis, one based on the detection of microsatellite instability (MSI) by PCR and the other based on the detection of protein expression of the MMR genes using immunohistochemistry (IHC). The objective of this study was to evaluate the concordance between IHC and MSI in tumors from 18 LS patients with known pathogenic germline variants in MMR genes (MLH1, MSH2, PMS2 and MSH6). Methods: The MSI testing was performed using the five gene Bethesda panel (BAT25, BAT26, D2S123, D5S346, D17S250) while the IHC testing was done with the use of a standard 4 antibody panel (MLH1, MSH2, PMS2 and MSH6). Results: High concordance of the two methods was observed in 13/18 (72.2%) patients, mainly with disruptive mutations in the МLH1, MSH2 and PMS2 genes. Inconsistent results were obtained in 5/18 (28.8%) patients, of whom two had a positive result only with the use of the PCR method [carriers of MLH1 c.62C > T (p.Ala21Val) and c.244A > G (p.Thr82Ala) missense variants], other two had a positive result only with IHC [carriers of MSH6 c.3514dupA (p.Arg1172LysfsTer5) and c.2384T > C (p.Ile795Thr)] and one patient had normal results using both methods (carrier of MSH6 c.457+1G > T splice site mutation that results in exon 3 skipping). A positive predictive value of either MSI or IHC used as a single methods for screening was 83.3%, which indicates that a substantial number of cases with MMR tumors can be misdiagnosed by using only either one or the other of these two methods. Conclusions: These results have a potential implication not only for LS screening in CRC patients, but also for the detection of the MMR deficiency in patients with various tumors that might benefit from the checkpoint inhibitor immunotherapy. The use of extended MSI NGS panels might provide a higher sensitivity for the detection of MMR deficiency compared to the standard MSI or ICH testing.

Idiopathic infantile hypercalcemia: mutations in SLC34A1 and CYP24A1 in two siblings and fathers

2020 ◽  
Vol 33 (10) ◽  
pp. 1353-1358
Author(s):  
Ayla Güven ◽  
Martin Konrad ◽  
Karl P. Schlingmann
Keyword(s):  
Vitamin D ◽  
Stop Codon ◽  
Gene Mutations ◽  
Splice Site Mutation ◽  
Heterozygous Mutation ◽  
High Dose ◽  
Loss Of Function ◽  
Site Mutation ◽  
Medullary Nephrocalcinosis ◽  
Idiopathic Infantile Hypercalcemia

AbstractObjectivesBoth CYP24A1 and SLC34A1 gene mutations are responsible for idiopathic infantile hypercalcemia, whereas loss-of-function mutations in CYP24A1 (25-OH-vitamin D-24-hydroxylase) lead to a defect in the inactivation of active 1.25(OH)2D; mutations in SLC34A1 encoding renal sodium phosphate cotransporter NaPi-IIa lead to primary renal phosphate wasting combined with an inappropriate activation of vitamin D. The presence of mutations in both genes has not been reported in the same patient until today.Case presentationHypercalcemia was incidentally detected when a 13-month-old boy was being examined for urinary tract infection. After 21 months, hypercalcemia was detected in his six-month-old sister. High dose of vitamin D was not given to both siblings. Both of them also had hypophosphatemia and decreased tubular phosphate reabsorption. Intensive hydration, furosemide and oral phosphorus treatment were given. Bilateral medullary nephrocalcinosis was detected in both siblings and their father. Serum Ca and P levels were within normal limits at follow-up in both siblings. Siblings and their parents all carry a homozygous stop codon mutation (p.R466*) in CYP24A1. Interestingly, both siblings and the father also have a heterozygous splice-site mutation (IVS6(+1)G>A) in SLC34A1. The father has nephrocalcinosis.ConclusionsA biallelic loss-of-function mutation in the CYP24A1 gene was identified as responsible for hypercalcemia, hypercalciuria and nephrocalcinosis. In addition, a heterozygous mutation in the SLC34A1 gene, although not being the main pathogenic factor, might contribute to the severe phenotype of both patients.

Sign in / Sign up

Export Citation Format

Share Document