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Genetic Basis of Nystagmus: Review of Literature About the Affected Families from Balochistan Province

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Genetic Basis of Nystagmus: Review of Literature About the Affected Families from Balochistan Province REVIEW ARTICLE ISRA MEDICAL JOURNAL | Volume 9 - Issue 6 | Nov - Dec 2017 Genetic Basis of Nystagmus: Review of literature about the affected families from Balochistan Province Muhammad Musawir Khan Kakar1, Abdul Malik Tareen2, Imran Shabir3, Hafeezullah Khan1, Naqeeb Jogizai4, Waqar Arshad4 ABSTRACT Nystagmus is an ocular disorder which is defined as an uncontrolled oscillatory moment of the eyes. Familial Nystagmus with certain eye disorders are heterogeneous based on genetic analysis and very little is known about the underlying mechanism. Studies on different genetic issues show that Pakistan has a populace with a flexible pool of genetics engaged with causing maladies and, in this manner; is inclined to be explored for novel Genes. Although various genes have been reported to be the cause of nystagmus either explicitly or implicitly. To date various genes have been put on record that are responsible to cause nystagmus that include but are not limited to FRMD7, TYR, CNGA3, GPR14, NYS3, NYS4, NYS5, NYS6, NYS7, CNGA3 & CNGB3, GNAT2, PDE6C & PDE6H .yet Pakistan is in a dire need of molecular investigation of nystagmus. We therefore reviewed in this article the genes pool responsible for causing nystagmus. KEYWORDS: Nystagmus; pathophysiology; Familial Nystagmus, heterogeneous, novel gene. HOW TO CITE THIS: Kakar MMK, Tareen AM, Shabir I, Khan H, Jogizai N, Arshad W. Genetic Basis of Nystagmus: Review of literature about the affected families from Balochistan Province. Isra Med J. 2017; 9(6): 435-38 This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. INTRODUCTION eyes, defined as repetitive to and fro movement. It may be physiological or pathological and may be congenital or In this article, we have attempted to review the genetic basis acquired.1 of nystagmus. We have explained nystagmus and the causes TYPES OF NYSTAGMUS behind nystagmus. In the beginning we have discussed the Nystagmus is generally classified into three broad categories: types of nystagmus, then this is followed by Discussion on a) Congenital / infantile nystagmus: It is an x-linked genetics involved in nystagmus including a comprehensive disorder of the eyes which happens at birth or assessment of the different genes (FRMD7, TYR, CNGA3, soon after. Congenital nystagmus may be found GPR14, NYS3, NYS4, NYS5, NYS6, NYS7, CNGA3 & CNGB3, linked to other disorders in a syndromic form.2-4 GNAT2, PDE6C & PDE6H), their likely role in the development b) Induced nystagmus. This nystagmus type, as the name of nystagmus furthermore, the subtle elements of the variants indicates, is physiologically induced and the probable causes of published in these genes have been reviewed. which are: thermal stimuli, visual stimuli, and rotation of the body Clinical Manifestations Nystagmus is a- an ailment of the c) Acquired nystagmus: It is the form of nystagmus which occurs due to the factors other than inducing factors such as drug toxicity. 1. M.Phil. Scholar of Microbiology Spontaneous Nystagmus: Spontaneous nystagmus has been 2. Professor of Microbiology defined as that nystagmus which appears in the upright University of Baluchistan, Quetta, Baluchistan, Pakistan position of the head, in darkness and at least 3 feet away from 3. Assistant Professor of Bioinformatics and Biotechnology any form of stimulus. It has not been included in the above 4. Ph.D. Scholar of Bioinformatics and Biotechnology classification. Islamic International University Islamabad, Pakistan Etiopathogenesis: Clinically, nystagmus can be characterized by the plane/s of oscillation, the direction/s of gaze at which Correspondence to: it occurs, the degree of conjugacy. A reasonable indicator of Muhammad Musawir Khan Kakar the nystagmus can be obtained by merely viewing the eyes. M.Phil. Scholar of Microbiology This can be further supplemented by the use of Frenzel’s University of Baluchistan, Quetta, Baluchistan, Pakistan glasses, electro-nystagmus consist of a slow drift of the eyes Email: [email protected] in one direction followed with a fast corrective movement in the neutral position, and it is termed as jerk nystagmus. When Received for Publication: 17-10-16 the eyes oscillate like a sine wave, the nystagmus is termed as Accepted for Publication: 09-10-17 pendular nystagmus. 435 Muhammad Musawir Khan Kakar et al. ISRA MEDICAL JOURNAL | Volume 9 - Issue 6 | Nov - Dec 2017 DISCUSSION FRMD7-FERM DOMAIN CONTAINING 7: The human FRMD7 gene contains 12 exons, encodes a 714-buildup polypeptide. 28 A cohort study that was conducted particularly on blind nystagmus causing transformations have been distinguished in or partially sighted children who were over 15 years in the FRMD7 gene up to now .a locus for x-linked sporadically Denmark estimated the prevalence of nystagmus. A study overwhelming CIN revealed by kerrison et al. Xq26-q27 in 3 was conducted in the Netherlands among 220,802 army clans and a clan with X-Linked overwhelming CIN by Cabot et recruits, who were primarily excluded from service due to al. at Xp11.4-p11.3 accounts for such a mutation.2, 3 their deteriorated visions. It was later reported that 117 were In a recent study in 2015 carried out by Jae-Hwan Choi and eventually discharged because of nystagmus.5 Another study his co-workers, they identified a novel start codon mutation conducted showed that elementary school children who were within the FRMD7 gene of 2 Korean families. They revealed in first grade in Malmö, Sweden between 1941 and 1959. The that mutation spectrum of FRMD7 was the causative agent result of this study showed that a total frequency of 1 in 1500 of IIN.9 In 2011, Arif O. Khan and his co-workers carried out a children; boys: 1 in 1000 and girls: 1 in 2800.6 study on a family in soudi arabia. They found mutation in two overwhelmed individuals in their findings that inFRMD7 splice GENES INVOLVED IN CAUSING NYSTAGMUS mutant (c.1050 + 5 G>A).10 In yet another study carried in 2012 by Hu Ying in a long four generation Chinese family in which Many of the congenital or hereditary pigmentary disorders of a novel mutation was detected preceding exon3 of FRMD7 in the skin are basically associated with pigmentary abnormalities affected individuals whereas healthy individuals had no such in the eye, such as changes in pigmentation of the fundus or iris mutations that confirms the involvement of FRMD7 in causing heterochromia. However, more commonly, the associated eye congenital nystagmus.11 finding is actually a defect in ocular motility, i.e., strabismus and nystagmus, recognizing the neuro-developmental etiology GPR143 GENE: The human GPR143 gene - plays a signaling leading to nystagmus is of prime significance for understanding role, consists of 9 exons which encode a 439-kDa protein of the pathophysiology of nystagmus. Genetic heterogeneity 404 aa.12 About more than 100 mutations of GPR143 have is well established in Nystagmus and so far various genes been identified. Most of the alterations in this gene have been (FRMD7, TYR, GPR14, NYS3, NYS4, NYS5, NYS6, NYS7, CNGA3 reported to be associated with OA but some mutations have & CNGB3, GNAT2, and PDE6C & PDE6H) have been discovered. been noted to be associated with CN.13 In a very recent study Mutations in these genes are thought to possess an important in 2016, Liu J conducted a study on a large sixth-generation role to play in causing nystagmus. Chinese family and characterized nystagmus .in their study they reported a new gene other than the FRMD7 gene and reported a novel large deletion in exon 3 -9 of the GPR143 gene TYR GENE: TYR is a gene that instructs the production of a suggesting that not only FRMD7 but variations in other genes protein called tyrosinase which is an enzyme responsible for such as GPR143 are also one of the main causes of nystagmus.14 various steps in melanin production in specialized cells called melanocytes. Melanin is a pigment that confers skin, hair, and NYS3 GENE & NYS4 GENE: It is a gene that is present at a locus nails a specific colors.it is also found in retina, where it plays on chromosome number 13.in 2003, Ragge NK. et al. carried a role in normal vision. Thus any mutations in TYR can cause out a phenotypic study of a unique four generation family with problems to the vision system such as nystagmus. To date nystagmus. They identified affected family members who had almost 320 mutational changes have been noticed for TYR developed nystagmus in the first 24 months of life. Haplotype gene in various ethnic populace around the world reported construction and analysis of recombination events linked the in the Human Genome Mutation Database (HGMD). Changes disorder to NYS4 on chromosome 13q31-q33.15 in the TYR gene is a fundamental reason behind albinism of various types i.e. type 1 Oculocutaneous Albinism termed as CNGA3 & CNGB3, GNAT2, PDE6C & PDE6H GENE: Mutations type 1A (OCA1A). in any of these genes cause a disease known as Achromatopsia In a study, Faravareh Khordadpoor-Deilamani, et al. in 2015 (ACHM) -a congenital, retinal disease that ultimately leads to found TYR gene mutations which were identified in 14 (app. nystagmus.. Zelinger L and his co-workers in 2015 identified 60%) albinism patients.7 Another study was carried by Liu N et 148 ACHM patients from 57 Israeli and Palestinian families; al. In 2014. In their study they screened a total of 30 individuals there were 16 CNGA3 mutations (5 novel) in 41 families and 5 with 100 healthy individuals as control for mutations in TYR CNGB3 mutations (1 novel) in 8 families.16 gene from a Chinese family affected with OCA.
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