Diagnostic challenges in a CMMRD patient with a novel mutation in the PMS2 gene: a case report.
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ABSTRACT: Background
Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessive condition, which is caused by biallelic mutations in mismatch repair genes: MSH2, MLH1, MSH6, and PMS2.Case presentation
We reported a unique case of an 11-year-old Chinese girl with colorectal polyposis and café-au-lait macules who had no obvious family history of Lynch syndrome-associated tumors, followed by brain gliomas and colorectal carcinoma five years later. The diagnosis of CMMRD was based on gene sequencing analysis showing a homozygous deletion NM_00535.5:c.1577delA (p.Asp526fs) in exon 11 of the PMS2 gene. Although the patient underwent surgery and radiation therapy, and close surveillances including radiological, endoscopic and hematological screening have been recommended, she died of the exacerbation of neurological symptoms at the age of 18.Conclusions
We identified a novel homozygous deletion in the PMS2 gene in a CMMRD patient with complex clinical features.
SUBMITTER: Tan S
PROVIDER: S-EPMC8274000 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Introduction Thalassemia is a genetically complex disorder that evolves from a mutation in the beta chain of hemoglobin. Much work has been done on the common mutations, but some rare mutations have been found that impact and diversify the disease spectrum. Case presentation Our case report is on a young adult who presented with anemia, gall stones, and off-and-on transfusion dependency. A detailed workup revealed that the patient was suffering from thalassemia intermedia. The interesting finding was that the patient, product of non-consanguineous marriage was homozygous for beta thalassemia mutation on genetic analysis. A detailed genetic analysis of the parents revealed them as carriers for the same mutation. It was found that patient was homozygous for a rare and novel mutation −88(C > A)[HBB:c.-138C > A] on whole gene sequencing. Discussion The area of genomics in thalassemia is rapidly growing, and our case report aims to update the current knowledge of thalassemia's genomic information in Pakistan. The mutation found in our patient was −88(C > A)[HBB:c.-138C > A], and the data provided by the National Library of Medicine for this mutation as Allele ID: 380597 and variant type of single nucleotide variant shows that only ten such cases exist in the world with this rare mutation. Our case would be the 11th case in the world and 1st in Pakistan according to the literature, reporting above mentioned mutation. Conclusion Further translational study is required to accurately utilize genomic data as an instrument of precision treatment in thalassemia patients, especially in underdeveloped countries like Pakistan. Highlights • Thalassemia evolves from a mutation in the beta chain of hemoglobin transferred mostly from parents to children or rarely a de novo mutation might occur.• Globally there are more than 535 gene mutations in beta chain of hemoglobin with common ones in Pakistan being IVSI-1,IVSI-5, IVSII-1, del 619, Fr 8–9, Fr 16, Fr 41–42.• Our case report is about a thalassemia patient having a rare mutation in beta globin gene of hemoglobin on genetic analysis.
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