|Year : 1990 | Volume
| Issue : 4 | Page : 193-194
Genetic heterogeneity of Oguchi's disease
Jai Rup Singh
Human Genetics Laboratory, School of Life Sciences, Guru Nanak Dev University, Amritsar-143 005, India
Jai Rup Singh
Human Genetics Laboratory, School of Life Sciences, Guru Nanak Dev University, Amritsar-143 005
Source of Support: None, Conflict of Interest: None
An analysis of the cases reported in Punjab, India, indicates the presence of genetic heterogeneity of Oguchi's disease, for which autosomal recessive inheritance has been documented earlier. The autosomal dominant inheritance pattern of this disease is associated with incomplete penetrance and a distinct sex bias towards females. This recognition is important for genetic counselling.
|How to cite this article:|
Singh JR. Genetic heterogeneity of Oguchi's disease. Indian J Ophthalmol 1990;38:193-4
| Introduction|| |
Oguchi's disease, first described by Oguchi in 1907, is characterized by congenital, bilateral and stationary type of nyctalopia ,, at times also wrongly reported as hemeralopia.  It is associated with structural anomalies of the retina and diffuse yellow or grey colouration of the fundus. The normal colour of the fundus returns only after 2-3 hrs in total darkness. This disease is considered to be rare. The first European case with Oguchi's disease was documented in 1927.  the first American case in 1939  and the first Indian case in 1969.  It is known to be hereditary with autosomal recessive mode of inheritance  without any distinction being made in Type I, Type Ila or Type Ilb. However, an analysis of the cases reported in India indicates the presence of genetic heterogeneity in this disease.
| Comments and discussion|| |
The report of 19 cases of Oguchi's disease by Singh et al,  of which 10 belong to one city and three to a neighbouring township, supports the contention of-the authors that this disease may not be as rare as it is supposed to be. But their observation that the inheritance pattern of the disease is in conformity with that of autosomal recessive inheritance, as reported earlier in literature, appears to be incorrect. Their data are rather strongly in favour of autosomal dominant type of inheritance at least for their familial cases. These authors reported three families having ten affected in- dividuals distributed over two generatioons. Patients of two families exhibited Type I Oguchi's disease while that of the third family Type Ila. These three families are crucial, as all the individuals had been specifically examined for this disease by ophthalmologists. It is important because in the absence of thorough fundus examination and observation of Mizuo's phenomenon, there is every likelihood of a wrong diagnosis.  Enquiries from one of these authors revealed that within each of these three families, there were some normal individuals but their exact number is not traceable now.  If we reduce the data of these authors into the pedigree format, it will become obvious that the familial cases reported by them are not autosomal recessive In autosomal recessive mode of inheritance for rare diseases, the major characteristic features are:
(i) A higher incidence of consanguinity.
(ii) Parents are usually normal while 25% of the offspring is afflicted.
(iii) The probability of an affected homozygote marrying an heterozygote is extremely low
The reported three pedigrees [Figure - 1] reveal absence of consanguinity (as specifically mentioned by the authors). In two families (Nos. 2 and 3), the mothers are also similarlly affected and the number of affected individuals is much more than the expected 25% for recessive inheritance even after giving the due concession for some of the normal individuals reported in each sibship.
On the other hand, in autosomal dominant type of inheritance for rare diseases, the characteristic features are:
(i) Affected individuals have at least one similarly affected parent except in cases of incomplete penetrance.
(ii) 50% of the sibs are likely to be affected.
(iii) No higher incidence of consanguinity.
All the three pedigrees are more or less in conformity with these characteristics. The family No. 1 most likely exhibits the presence of incomplete penetrance. The sex and distribution of the affected individuals in these pedigrees also rules out the operation of .X-linkage but highlights the presence of sex influence. In familial cases, out of 10 affected individuals, 8 are females while amongst 9 isolated' cases, 7 are males and only 2 females. The presence of 9 additional isolated cases without any familial associations coupled with the significant sex differences between the two categories points to the operation of some other factors in the isolated cases than dominant type of inheritance only.
Considering Oguchi's disease to be genetic in origin, there could be several explanations for the isolated cases. A few of these cases could be of the dominant type with incomplete penetrance where their relatives, having milder symptoms may have escaped detection. Some could be of autosomal recessive type as already reported in the literature.  But the confirmation of it is not possible in the absence of complete familial data. Another possibility is that some of these isolated cases may be new mutants. However, as the incidence of Oguchi's disease is considered to be very low, the probability of new mutations occurring in such a high frequency is very remote. Alternatively, this disease is not a rarity in this region as is generally believed. A higher incidence of Oguchi's disease has also been reported for Japan. 
The main characteristic feature of Oguchi's disease in the absence of complete fundus examination is congenital stationary type of night blindness. Genetic heterogeneity for congenital stationary type of night blindness is obvious from the literature. For this purpose, autosomal dominant t e of inheritance has been frequently reported ,,, In addition, X-linked form in association with myopia has been recorded. , A bias towards females, as seen in the presented pedigrees, has also been recorded for congenital stationary blindness by Francois et al,  who reported a family of three generations where all four affected individuals were females. Moreover, the presence of different modes of inheritance for the same clinical entity is well documented, especially for ophthalmic disorders. Autosomal dominant and recessive types of corneal dystrophies ,, cornea plana ,, ectopic lentis , retinoblastoma, , dominant and X-linked types of megalocorneal,  autosomal dominant, recessive as well as X-linked types of congential cataracts ,, and retinitis pigmentosa ,, are some of the known examples.
In light of these observations,it is clear that Oguchi's disease like many other congenital ophthalmic conditions exhibits genetic heterogenity and has two distinct modes of inheritance; autosomal dominant as well as autosomal recessive. The dominant type being associated with incomplete penetrance and has a distinct sex bias towards females. This recognition of the genetic heterogeneity is important from the view point of proper genetic counselling.
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[Figure - 1]