ORIGINAL ARTICLE Year : 1993  Volume : 41  Issue : 1  Page : 2325 A genetic analysis of retinitis pigmentosa Jayashree Shanker^{1}, A Ramesh^{2}, ^{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: 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.
MATERIALS AND METHODS 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 LaurenceMoon 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(r1) P=a(r1) a(s1) 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+(1X) q(s1) Xspr+(1X)[(1pr)s] 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=1p RESULTS 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 nightblindness, the age of onset varying from birth to 47 years. Fortynine 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 noncontributory 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 [3],[5] The low `P' value obtained for the total and consanguineous data was a reflection on the presence of a large extent of nongenetic 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 Xlinked 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 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


