14 research outputs found
Clinical and genetic heterogeneity in Wilson disease - A review
Wilson disease (WD) is an inborn error of copper metabolism leading to its accumulation in liver, kidney and cornea. It is caused by a defective ATPase protein which is coded by ATP7B gene. It follows an autosomal recessive mode of inheritance with a prevalence of 1 in 30,000. WD shows varied clinical heterogeneity making clinical diagnosis a difficult task. The corneal Kayser-Fleischer (KF) ring is an important diagnostic criterion as it is invariably present in 95% of the WD cases. In this review, we discussed the varied clinical manifestations of WD which makes diagnosis a challenging process. Though genetic testing is a reliable technique to confirm clinical diagnosis, genotype-phenotype correlations are yet to be established. This could be attributed to the consanguinity and ethnic variation observed in the Indian population, suggesting genetic heterogeneity leading to clinical heterogeneity making diagnosis difficult. Further, genetic studies are warranted to establish genotype-phenotype correlations which can pave way for early diagnosis and treatment. Genetic testing will help in identifying pre-symptomatic siblings and other family members of the patient who should be advised for regular follow-up. A combination of clinical and genetic studies should be considered for proper understanding of disease manifestation and for making an early clinical diagnosis of WD
Genetic variations of \u3b2-MYH7 in hypertrophic cardiomyopathy and dilated cardiomyopathy
Context: Hypertrophic cardiomyopathy (HCM) is known to be manifested by
mutations in 12 sarcomeric genes and dilated cardiomyopathy (DCM) is
known to manifest due to cytoskeletal mutations. Studies have revealed
that sarcomeric mutations can also lead to DCM. Therefore, in the
present study, we have made an attempt to compare and analyze the
genetic variations of beta-myosin heavy chain gene (\u3b2-MYH7), which
are interestingly found to be common in both HCM and DCM. The
underlying pathophysiological mechanism leading to two different
phenotypes has been discussed in this study. Till date, about 186 and
73 different mutations have been reported in HCM and DCM, respectively,
with respect to this gene. Aim: The screening of \u3b2-MYH7 gene in
both HCM and DCM has revealed some common genetic variations. The aim
of the present study is to understand the pathophysiological mechanism
underlying the manifestation of two different phenotypes. Materials and
Methods: 100 controls, 95 HCM and 97 DCM samples were collected.
Genomic DNA was extracted following rapid nonenzymatic method as
described by Lahiri and Nurnberger (1991), and the extracted DNA was
later subjected to polymerase chain reaction (PCR) based single
stranded conformation polymorphism (SSCP) analysis to identify single
nucleotide polymorphism (SNP)s/mutations associated with the diseased
phenotypes. Results and Conclusion: Similar variations were observed in
\u3b2-MYH7 exons 7, 12, 19 and 20 in both HCM and DCM. This could be
attributed to impaired energy compromise, or to dose effect of the
mutant protein, or to even environmental factors/modifier gene effects
wherein an HCM could progress to a DCM phenotype affecting both right
and left ventricles, leading to heart failure
Genetic variants in post myocardial infarction patients presenting with electrical storm of unstable ventricular tachycardia
Electrical storm (ES) is a life threatening clinical situation. Though a few clinical pointers exist, the occurrence of ES in a patient with remote myocardial infarction (MI) is generally unpredictable. Genetic markers for this entity have not been studied. In the present study, we carried out genetic screening in patients with remote myocardial infarction presenting with ES by next generation sequencing and identified 25 rare variants in 19 genes predominantly in RYR2, SCN5A, KCNJ11, KCNE1 and KCNH2, CACNA1B, CACNA1C, CACNA1D and desmosomal genes - DSP and DSG2 that could potentially be implicated in electrical storm. These genes have been previously reported to be associated with inherited syndromes of Sudden Cardiac Death. The present study suggests that the genetic architecture in patients with remote MI and ES of unstable ventricular tachycardia may be similar to that of Ion channelopathies. Identification of these variants may identify post MI patients who are predisposed to develop electrical storm and help in risk stratification
Evaluation of Kayser–Fleischer ring in Wilson disease by anterior segment optical coherence tomography
Purpose: The purpose of the study is to present anterior segment optical coherence tomography (AS-OCT) as an alternative method of evaluating Kayser–Fleischer (KF) ring in Wilson disease (WD) not only by ophthalmologists but also by other clinicians dealing with WD. Materials and Methods: This was a retrospective case series of six WD patients with KF ring. Evaluation of KF ring was done by naked eye examination using torch light, slit lamp biomicroscopy (SL), and AS-OCT. SL examination was done using a narrow slit of the superior cornea. AS-OCT was done using the Optovue RTvue PremierTM device (Fremont, CA, USA). Results: AS-OCT revealed KF ring as an intense hyperreflective band at the level of Descemet membrane (DM). Color scale of AS-OCT showed KF ring as greenish/greenish yellow/orange yellow/yellowish/red band. Validation of AS-OCT findings was done by second ophthalmologist, medical gastroenterologist, surgical gastroenterologist, and neurophysician. After seeing the first observation, they could identify the AS-OCT features in all pictures with ease. Conclusions: This is the first observation of KF ring in WD on AS-OCT. On AS-OCT, KF ring is visualized as intense hyperreflectivity at the level of DM in the peripheral cornea. Further, studies are needed to evaluate the usefulness of AS-OCT in WD management
Linkage Disequilibrium plot for NOS3 polymorphisms in cases and controls: data is D′ values.
<p>Linkage Disequilibrium plot for NOS3 polymorphisms in cases and controls: data is D′ values.</p
Evaluation of Kayser–Fleischer ring in Wilson disease by anterior segment optical coherence tomography
Pairwise Linkage Disequilibrium estimates in DCM compared to controls.
<p>Pairwise Linkage Disequilibrium estimates in DCM compared to controls.</p
Haplotype frequency distribution among controls and cases.
<p>OR – Odds Ratio, CI – Confidence Interval.</p
Odds risk estimation of NOS3 polymorphisms in DCM compared to controls.
<p>OR – Odds Ratio, CI – Confidence Interval.</p