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Year : 1993  |  Volume : 41  |  Issue : 1  |  Page : 23-25

A genetic analysis of retinitis pigmentosa

1 Department of Genetics, Post Graduate Institute of Basic Medical Sciences, Taramani, Madras, India
2 Human Genetics Division, Department of Biostatistics (GSPH) University of Pittsburgh, Pittsburgh, P.A. U.S.A

Correspondence Address:
Jayashree Shanker
3/7 Anugriha Apts, Service Road, Domlur Layout, Bangalore - 560 071, India

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Source of Support: None, Conflict of Interest: None

PMID: 8225518

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The data consists of sixty probands affected with Retinitis pigmentosa. Syndromic cases were found in five percent of the RP probands. Segregation analysis was carried out on proband sibship data. The ascertainment probability was estimated at 0.5517. Analysis of the data by parental mating types of proband sibships indicated the presence of dominant forms of RP (2.05%). Analysis of proband sibships indicated the presence of low risk families in the Normal x Normal matings (45%) and in the consanguineous matings (40%). The hypothesis of recessive inheritance could be confirmed only in multiplex sibships (p = 0.383 +/- 0.0793). Data on proband matings though incomplete conformed in general to autosomal recessive gene hypothesis.

How to cite this article:
Shanker J, Ramesh A. A genetic analysis of retinitis pigmentosa. Indian J Ophthalmol 1993;41:23-5

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Shanker J, Ramesh A. A genetic analysis of retinitis pigmentosa. Indian J Ophthalmol [serial online] 1993 [cited 2023 Dec 11];41:23-5. Available from: https://journals.lww.com/ijo/pages/default.aspx/text.asp?1993/41/1/23/25629

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Retinitis pigmentosa (RP) is the name given to a group of diseases characterised by progressive visual loss, night blindness and abnormal or nonrecordable electroretinogram (E.R.G).

Two broad groups of pigmented retinopathies can be recognised : (i) primary RP in which the disease process is confined only to the eyes and (ii) secondary RP, where the pigmentary retinal degeneration is associated with the diseases involving single or multiple organ systems. Further classifica­tion within the groups is based on the nature of inheritance type and the pattern on the E.R.G.

Genetically, RP is heterogenous. Autosomal dominant with variable penetrance, autosomal recessive and X-linked forms are known to exist. Environmental agents like virus, drugs and trauma also cause symptoms as in genetic form of RP. Hence, careful diagnosis and detailed family studies are very important in determining the etiology of RP in a family. This in turn helps to provide accurate genetic counselling.

Several attempts have been made to resolve the genetic heterogeneity of RP. Whereas most studies were based on pedigree patterns alone [1],[2]a few reports have been published where the frequencies of the different RP types have been estimated by employing segregation analysis [3],[4],[5] In all these studies, the relative proportions of the different genetic and non-genetic cases of RP vary from population to population and is due largely to the difference in their genetic compositions.

In our present study, an attempt has been made to analyse the pedigree data by segregation analysis.

  Materials and methods Top

Patients who were affected with RP and attending two private eye clinics and Government Eye Hospitals in Madras city comprised the material for this study. Altogether, 60 cases were ascertained. Clinical information on probands were obtained from the records available with the doctors.

Two sets of data were analysed (1) Proband sibship and (2) Proband matings. Of the 60 probands ascertained there were three syndrome cases. Two patients with Laurence-Moon- Biedl syndrome showed RP, mental retardation, obesity, polydactyly and hypogonadism. There was a single case of Usher's syndrome who had congenital deafness in addition to RP. As syndromes represent separate genetic entities, they were excluded from segregation analysis.

The first set of data was analysed through segregation analysis based on the mating type of the proband parents. Two types of matings were observed in our data:

(1) Normal x Normal (N x N); (2) Affected x Normal (A x N). The former mating type was tested for autosomal recessive inheritance and the latter for autosomal dominant inheritance.

Segregation analysis involves the estimation of three important parameters (i) ascertainment probability (Ir )-- the probability that an affected is a proband; (ii) segregation frequency (p) - the probability of an affected in a given mating type (iii) proportion of sporadic cases (X). The estimation of these parameters were carried out as per Cavalli - Sforza and Bodmer band Morton.[7]

The estimation of lr is needed for the unbiased estimation of the other two parameters i.e. p & x and is calculated by using Fisher's extension of Weinberg's proband method:

a (a - 1) where a = no.of probands and

Ir = r = no. of affected in a sibship a(r-1)


a(s-1) Where a= no. of probands

r= no.of affected

s= sibship size

In this methods each sibship is counted once for each proband, leaving out the proband himself.

Proportion out the proband himself.

Proportion of sporadic cases (X) :

P(r=1/r>0)= sPr (X+(1-X) q(s-1)


Where P (r=1/r>0)=probability of one affected given that the number of affected >0

S=sibship size; r=no.of affected;q=1-p

  Results Top

In a total of 60 index RP patients belonging to 52 families, there were three syndrome cases. Of the remaining 57 probands, 17 had other ocular defects like squint, cataract, myopia, etc. and 2 cases showed involvement of extraocular symptoms like hearing loss, diabetes, rheumatic fever etc. In 5 cases, both ocular as well as extraocular defects were observed. Forty eight probands complained of night-blindness, the age of onset varying from birth to 47 years.

Forty-nine sibships were available for segregation analysis. Two types of parental mating type were observed in the data (1) Affected x Normal (2) Normal x Normal

A single family belonging to the first category with two out of four children affected (50%) confirmed to autosomal dominant inheritance [Figure 1].

Among the remaining 48 sibships belonging to N x N mating type, two single sibship families (S = 1) were excluded as they were non-contributory to segregation analysis; of the two single sibship families one belonged to N x N mating and the other to consanguineous mating. Segregation analysis has been carried out on 46 N x N matings; 26 consanguineous N x N coatings and 13 multiplex families independently [Table. 1].

The RP index cases were ascertained through multiple incomplete selection. The n value was estimated to be 0.5517 for all N x N matings, 0.2857 for consanguineous matings and 0.5714 for the multiplex subsamples.

The estimated P value for the total N x N matings (P = 0.142 0.032) and consanguineous data (P = 0.138 + 0.0391) was low and not in agreement with the value P = 0.25 expected for autosomal recessive inheritance. However, the multiplex subsample with a value of P = 0.383 f 0.0783 conformed to the recessive gene hypothesis. Assuming the low P value in the total data to be due to the inclusion of a large number of simplex cases, its estimation was carried out. The deviation between the observed (33) and estimated (20.8) number of simplex cases was highly significant (XI with 2d.f is 16.82; p < 0.01) proving our hypothesis.

The proportion of sporadic cases for N x N matings and consanguineous matings were calculated to be 0.45 and 0.40 respectively.

There were 25 matings involving the proband, all belonging to the A x N mating type. Of the 22 matings which had produced offsprings, only one family had two affected-children.

  Discussion Top

The genetic heterogeneity of RP has been well substantiated in several studies by the presence of different patterns ofinheritance and the occurrence of syndromes associated with RP. RP patients affected with Laurence-Moon-Biedl-Syndrome (LMB) constituted about 3.3 % of the sample. This was similar to the estimation of 3.6 % observed in 138 index patients of RP in Birmingham U.K' In one patient affected with this syndrome, independent segregation of polydactyly, one of the characteristic traits of LMB syndrome was seen to occur among the patient's sibs and not expressed by the patient herself.

At least two modes of inheritance namely autosomal dominanant and autosomal recessive are apparent among the RP cases observed. Only a single family with 50 % affected chidren conformed to autosomal dominant category.

The non-compatibility of recessive inheritance for all N x N matings as observed in the study was also indicated by a low `P' value in several independent studies [3],[5] The low `P' value obtained for the total and consanguineous data was a reflection on the presence of a large extent of non-genetic cases. This was confirmed by the estimation of 45 % and 40% of sporadic cases in the two samples respectively.

The compatibility of autosomal recessive inheritance only among the multiplex sibships as noted in our study was also reported by Boughman and Fishman. [5]

The probability of the occurrence of X-linked cases in multiplex families was left undetected due to small sample size (n = 13), insufficient pedigree information and lack of detection in the female parent of the male - only affected sibships.

Among the proband matings, except one family with two affected children, none of the other offsprings showed any symptoms of the disease. As the mean age of all offspring in the proband matings is only 14.7 years, this probably is a reflection on the late age of onset of the disease.

  Acknowledgements Top

The authors wish to thank Dr.Ravi. K & Dr. Agarwal for providing the addresses and clinical details of the patients during the course of the investigation. The financial assistance given by the Council of Scientific and Industrial Research is gratefully

acknowledged by J.Shanker.

  References Top

Fishman GA. Retinitis pigmentosa - genetic percentages. Arch Ophthalmol. 96, 1978.  Back to cited text no. 1
Bundey S and Crews J. A study of Retinitis pigmentosa in the city of Birmingham. J Med Genet. 21 : 417 - 420, 1984.  Back to cited text no. 2
Boughman JA, Michael CP and Walter EN. Population genetic studies ofRetinitis pigmentosa. Am J Hum Genet. 32: 223-225, 1980.  Back to cited text no. 3
Jay M. On the heredity of Retinitis pigmentosa. Br J Ophthalmol. 66 : 405-416, 1982.  Back to cited text no. 4
Boughman JA and Fishman GA. A genetic analysis of Retinitis pigmentosa. Br J Ophthalmol. 67 : 449 - 459, 1983.  Back to cited text no. 5
Cavalli - Sforza LL and Bodmer MP. Segregation and linkage analysis in human pedigrees and the estimation of gene frequencies, in the genetics of human populations. Freeman, San Francisco. 851 - 890, 1971.  Back to cited text no. 6
Morton NE. Genetic tests under incomplete ascertainment. Am J Hum Genet. 11: 1, 1979.  Back to cited text no. 7


  [Figure - 1]

  [Table - 1]


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