Polymorphism

CYP3A418 and CYP3A53 single nucleotide polymorphisms in an Azerbaijani population

Nigar Karimova, Aypara Hasanova, Bayram Bayramov — Sun, 10 Apr 2022 00:00:00 -0600

Aim: The human cytochrome CYP3A isoenzymes collectively cover the largest portion of the liver CYP protein, where they play a crucial role in the metabolism of 45-60% of all drugs. Among the SNPs of CYP3A isoforms, CYP3A4*18 andCYP3A5*3 variants are the most common allelic variations, which may play a significant role in the metabolism of many drugs. The aim of this study was to identify the frequency of both CYP3A4*18 and CYP3A5*3 polymorphisms in the Azerbaijani population.

Methods: We identified CYP3A4*18 and CYP3A5*3 allelic and genotype frequencies in 100 Azerbaijani individuals by using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique. The results were confirmed by next-generation and Sanger sequencing.

Results: The CYP3A5*3*/3* allele frequency was 97.5% (95 out of 100), with the *1 allele frequency being 2.5% (5 out of 100). All samples (100/100) were wildtype for the CYP3A4*18 allele.

Conclusion: In conclusion, this small-scale study suggests that 95% of Azerbaijani individuals with CYP3A5*3/*3 genotype might fail to express CYP3A5 protein. Therefore, our results highlight the importance of genotyping of CYP3A5*3 and CYP3A4*18 as well as demonstrate a demand for further investigations to evaluate their clinical relevance using a larger sample size.

A novel mutation (c.1966C>T; p. Gln656Ter) in the COL7A1 gene identified in a case of dystrophic epidermolysis bullosa by whole exome sequencing

Thu, 05 May 2022 00:00:00 -0600

Epidermolysis bullosa (EB) is an inherited disorder. It involves a heterogeneous group of the rare genetic dermatoses are characterized by the mucocutaneous brittleness and the blister development, which are often inducible by the minimal trauma. A wide-ranging phenotypic diversity has been defined, with possibly severe extracutaneous appearances, morbidity and the mortality in some cases. In this study, we have documented a case of the EB with a novel variant (c.1966C>T; p. Gln656Ter) in the COL7A1 gene detected by whole exome sequencing. This novel mutation has been authenticated by Sanger sequencing. This case highlights the importance of whole exome sequencing for confirmatory molecular diagnosis and adds a novel variant (c.1966C>T; p. Gln656Ter) to the genotypic spectrum of COL7A1 gene mutations in epidermolysis bullosa.

Identification of a novel mutation (c.1172_1181 del TGGTGCAAGC (p.Leu391fs) in the CUL7 gene in a patient of 3M Syndrome

Priyanka Vishwakarma, Ashish Dubey, Deepika Kalo, Vishal Mishra — Sun, 26 Jun 2022 00:00:00 -0600

3-M syndrome is a disorder characterized by the skeletal abnormalities including the short stature and unusual facial features. The affected people have low birth weight and length and remain much smaller than others in their family members, growing to an adult height of approximately 4 feet to 4 feet and 6 inches. In this study, we report a novel frameshift mutation (c.1172_1181delTGGTGCAAGC; p. Leu391fs) in the CUL7 gene in a patient of the 3M Syndrome. We performed the whole exome sequencing and after the identification of likely pathogenic variant, we validated the mutation with Sanger sequencing method. As per the public databases, this variant has been not reported till date. This study identified a novel frameshift mutation (c.1172_1181delTGGTGCAAGC; p. Leu391fs) in the CUL7 gene in a patient of the 3M Syndrome. The study also highpoints the clinical utility of exome sequencing in the definite diagnosis of the provisionally diagnosed genetic disorders whose ultimate diagnosis is important specially in the cases of consanguineous marriage.

Identification of c.286C>T mutation in the SLURP1 gene in a patient with Mal de Meleda from India

Gaurav Gupta, Gargi N Deshmukh, Vaggu Anand Kumar, Vadlamudi Raghavendra Rao — Sat, 18 Mar 2023 00:00:00 -0600

Mal de Meleda (MDM, OMIM#248300) is a very rare autosomal recessive skin disease caused by mutations in the SLURP1 gene. It is characterized by classical progressive transgradiens hyperkeratosis of the palms and soles, hyperhidrosis and minor symptoms such as perioral erythema, hyperkeratosis on elbows and knees, pseudo-ainhum, and nail abnormalities. Here, we report a SLURP1 mutation (NM_020427.2: c.286C>T) in a 38 years old Indian male with Mal de Meleda that is compatible with severe clinical features of patients reported from Croatia and Korea with the same mutation.

Genetic polymorphisms and their role in incidence of Non-alcoholic fatty liver disease

Akriti Gupta, Sudeep Gautam, Chakrapani S Inavolu — Wed, 27 Jul 2022 10:52:58 -0600

Non-alcoholic fatty liver disease (NAFLD) is one reason for chronic liver disease all over the world, be it the steatosis, nonalcoholic steatohepatitis (NASH), advanced hepatic fibrosis, cirrhosis, or hepatocellular carcinoma. The increasing prevalence of NAFLD is not clearly understood, but it is an established fact that metabolic abnormalities like diabetes, dyslipidemia, glucose impairment and obesity contribute significantly in the onset and progression of NAFLD. Genetics, nutritional factors and life style habits contribute to this. It is not understood how genetic factors play a role in triggering the pathogenesis and progress of NAFLD. In the present review, we debate the recent facts of the genetic basis of NAFLD induced by glucose homeostasis, lipid metabolism, oxidative stress, and related cytokines.

A review on genetic polymorphisms associated with splenic hemangioma.

Venkata Aksheena Varahi Vedam, Mohan Krishna Ghanta — Tue, 02 Aug 2022 10:45:11 -0600

Splenic tumours are uncommon compared to cancers of other parenchymatous organs. Hemangiomas are characterized as nonlymphocytic tumours. Though splenic hemangiomas are rare, they are caused by melanoma, breast cancer and lung cancer metastasis. This review identifies a few genetic polymorphisms that contribute to spleen cancer in this context.

A novel mutation (c.2762_2763insG; p.Pro923fs) identified in a patient with Alport Syndrome

Priyanka Vishwakarma, Ashish Dubey, Deepika Kalo, Vishal Kumar Mishra — Tue, 28 Feb 2023 04:13:20 -0700

Background: Alport syndrome is a genetic condition characterized by kidney disease, hearing loss, and eye abnormalities. People with Alport syndrome experience progressive loss of kidney function. Almost all affected individuals have blood in their urine (hematuria), which indicates abnormal functioning of the kidneys. Many people with Alport syndrome also develop high levels of protein in their urine (proteinuria). The kidneys become less able to function as this condition progresses, resulting in end-stage renal disease (ESRD).

Case presentation: A 2-year-old male patient had come to a clinic with the complaints of the developmental delay and the self-mutilation behavior. The clinician’s suspected Alport Syndrome on the basis of the clinical features. Parents were married consanguineously.

Results: We undertook exome sequencing analysis and identified a novel heterozygous mutation (c.2762_2763insG; p. Pro923fs) in the COL4A4 gene in this patient with Alport syndrome. The pathogenic mutation was confirmed by Sanger sequencing method. As per the genomic databases, this variant has been not reported till date.

Conclusions: This study identified a novel mutation in the COL4A4 gene in Alport syndrome, which will help in genetic diagnosis of such cases.