Volume 7, Issue 1 (February 2020)                   IJML 2020, 7(1): 9-14 | Back to browse issues page

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Beigi F, Vahidi Mehrjardi M Y, Manaviat M R, Ashrafzadeh H R, Ghasemi N. Study of Patterns of Inheritance in Affected Patients with Retinitis Pigmentosa in Iranian Populations. IJML. 2020; 7 (1) :9-14
URL: http://ijml.ssu.ac.ir/article-1-326-en.html
Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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The  prevalence of retinitis pigmentosa (RP)  is reported to be 1 case per 3000 to 7000 individuals [1]. At first, RP disease was described in 1853 [2]. RP is the most common heterogeneous group of inherited retinal disorders caused by damage to the light-sensitive rods and cones located in the retina, the back part of eyes. Rods, which provide side (peripheral) and night vision, are affected more than the cones that provide color and clear central vision [3, 4]. The first sign of affected individuals is night blindness, followed by decline of the peripheral visual field known as tunnel vision [3]. If RP disease involved vision alone, it is referred to as nonsyndromic RP and comprises about 70-80% of RP patients, are included but if the disease occurs systemically, it is termed syndromic RP. The most common forms of syndromic RP are Usher syndrome and Bardet-Biedl syndrome [5]. Bardet-Biedl syndrome is RP with autosomal recessive pattern characterized by cardinal features of postaxial polydactyly, retinitis pigmentosa, kidney defects, obesity and mental retardation as well as hypogonadism [6]. Usher syndrome is RP with hearing disorders and congenital [7]. Several methods for classifying RPs exist including electroretionogram test that measures electrical responses of photoreceptors in retina; ophthalmoscopic (fundoscopic) examination to distinguish degenerative changes in retina and retinal pigment epithelium and patterns of inheritance [8]. To date, over 260 genes have been involved in inherited retinal disorders. Among these, 88 genes have been identified to be associated with non-syndromic RP. At least 29, 54, and 5 genes/loci have been described to induce autosomal dominant RP (adRP), autosomal recessive (arRP), and X-linked (XLRP), respectively (RetNet database; https://sph.uth. tmc.edu/RetNet/). Next generation sequencing is one of the best approaches for identification of the genetic causes of Mendelian inherited RP [9]. Mutations in some of genes cause arRP pattern including CEP290, CRB1, ABCA4 and USH2A [6]. Pattern of adRP is the mildest inheritance pattern [10]. The genes responsible for mutations with adRP are RHO, RP1, PRPH2 and PRPF31 [6]. The genes that account for xIRP are RPGR and RP2 [6] (Table1). Vision defects caused by the mutations may be associated with apoptosis, light damage, ciliary transport dysfunction, and endoplasmic reticulum stress pathways. Common result of the pathways is rod photoreceptors loss [11].
Material and Methods
Thirty Iranian families affected with RP referred to the Genetics Clinic of the Research and Clinical Center for Infertility in Yazd Medical Sciences University from 2010-2016. This study was approved by the Ethics Committee of Shahid Saduoghi University of Yazd Medical Sciences. All the subjects provided written informed consent.
Table 1. The most common genes responsible for mutations with different patterns of inheritance
Genes Protein Patterns of inheritance OMIM Mutations
RHO Rhodopsin adRP 180380,613731 161
RPGR X-linked retinitis pigmentosa GTPase regulator   300029,312610 151
PRPH2 Peripherin-2 adRP 179605,608133 123
RP1 Oxygen regulated protein 1 adRP 180100,603937 67
RP2 Retinitis pigmentosa 2
X-linked 300757,312600, 76
PRPF8 Pre-mRNA-processing-splicing factor 8 adRP 600059,607300 21
USH2A Usherin arRP 608400,613809 392
NR2E3 Nuclear receptor
subfamily 2 group E3
adRP 604485,611131 45
CRX Cone-rod otx-like
homeobox transcription
adRP 120970,602225, 51
beta subunit
arRP 180072,613801 39
RPE65 Retinoid isomerohydrolas adRP:
180069,613794 134
EYS Eyes shut/spacemaker
(Drosophila) homolog
arRP 602772,612424 118
BEST1 Bestrophin 1 adRP:
607854,613194 232
CRB1 Crumbs homolog 1 arRP 600105,604210 183
CLRN1 Clarin-1 arRP 606397,614180 23
RDH12 Retinol dehydrogenase 12 adRP:
607854,613194 66
ABCA4 ATP-binding cassette
transporter – retinal
arRP 601691,601718 680
PRPF31 Human homolog of yeast
pre-mRNA splicing
factor 31
adRP 600138,606419 65
adRP=Autosomal dominant retinitis pigmentosa; arRP= Autosomal recessive retinitis pigmentosa
Full medical and family histories were taken from all families’ members. The pedigree chart from all of the Iranian families was displayed and ophthalmologic examinations were performed. The samples were divided into two groups: group 1 including patients with non-syndromic RP, without systemic involvement, and group 2 including patients with syndromic RP. The clinical symptoms and inheritance patterns in families were checked out.
In the present study, almost all of the patients in the families affected with RP were born from consanguineous marriages and unaffected parents. Ophthalmological examination revealed visual disturbance during the first decade of life, and visual acuity and visual fields declined with increasing age in affected individuals of the family. Progressive peripheral visual loss and fundus photography indicated extensive bone spicule in periphery, narrowing arteries and veins, and pale and waxy optic disc. The samples included females (53%) and males (47%). Molecular studies performed showed the patients suffering from Usher syndrome, Bardet-Biedl syndrome, Posterior Column Ataxia with Retinitis Pigmentosa and a patient with Kreans-Sayer syndrome, a mitochondrial disease. Autosomal recessive inheritance pattern bore the highest rate of inheritance pattern among the patients (Table 2).
Table 2. Patterns of inheritance found in families
Pattern  of  inheritance Type of disease Prevalence (%)  
Systemic or syndromic RP Usher syndrome 3.3
Bardet-Biedl syndrome 6.6  
Non-syndromic RP Autosomal recessive RP 76
Autosomal dominant RP 23
X-linked RP 10
Mitochondrial 3.3
Digenic 0
RP=Retinitis pigmentosa

RP is the most common heterogeneous group of inherited retinal disorders [4]. RP is transmitted by all types of inheritance patterns mostly including autosomal dominant, autosomal recessive and X-linked forms. In addition complex and mitochondrial patterns occur rarely [12, 13]. The study of RP in the world has revealed predominant types of inheritance patterns to be different in each region [14]. In the present study, patients with autosomal recessive inheritance had the highest rate compared with patients having a different pattern of inheritance. Our results regarding pattern of inheritance revealed to be in line with that of reported from Norway study [15]. A study in 2013, also identified autosomal recessive as the most common pattern of inheritance. This study demonstrated the importance of the evaluation of the affected family with a different pattern of inheritance, and according to the type of RP and the technology used, mutations in 30-80% cases were detected [14]. Finding the pattern of RP inheritance is very important for pre-marriage and better following molecular base of the disease processes. Clinical findings, patterns of inheritance and genetic of patient is an important step in the diagnosis of RP disease.
Worldwide RP studies have showed the differences in predominant type of inheritance in each region. These differences may be cause to epidemiological diversity. In our study, we reported that autosomal recessive pattern was the most common pattern. This study demonstrated the requirement genetic studies in all populations to give an accurate prognosis of the disease. Identifying affected genes in rare disorders leads to an accurate genetic counselling and a better follow-up of the disease. Molecular and clinical studies expand prognostic information for clinician and family.
Conflicts of Interest
The authors declare no conflict of Interest.
We are thankful to the patients and their families for their cooperation. The results described in this paper were extracted from a Ph.D. thesis and this article was supported by Yazd University of Medical Sciences with the grant No. 4929.
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Type of Study: Research | Subject: Genetics/ Biotechnology
Received: 2019/08/24 | Accepted: 2020/01/13 | Published: 2020/01/30

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