Phenotype i Associated with Congenital Cataract in Japanese

H. OGATA, Y. OKUBO AND T. AKABANE

From the Blood Bank Section, University of Shinshu Medical School Hospital, Matsumoto and the Osaka Red Cross Blood Center, Osaka, Japan

A Japaneae family with two slblings of phenotype i is presented. Botb had a past history of surgical treatment for congenital cataract. In Japan, 18 individuals of phenotype i, including our case, have been found in ten unrelated families. Seventeen of them had congenital cataract. Cataract was not found in any of the 45 pheno- type I members In these families. It is briefly discussed why t b two linked and quite rare genes were found in combhatlon only in Japanese persons.

SINCE the recognition of the phenotype i by Wiener et ~ l . , ~ it has been confirmed that this phenotype is quite rare. Though the I-i system has been extensively investigated from the aspects of serology, less effort has been made for its heredity. Four nonrelated families have been reported which included eight individuals of phenotype i all suffering from congenital cataract.10 The linkage was mathematically established, unless it were a case of pleiotrophy. We recently encountered a family which included two individuals of phenotype i with poor vision and cataract. The Japanese literature was searched and it was found that in Japanese the phenotype i was quite often associated with eye disorders.

Case Report A 54-year-old Japanese woman was admitted

to U.S.M. Hospital because of adenocarcinoma of the right breast. Antineoplastic chemotherapy was instituted, and anemia and leukopenia devel- oped three weeks later. The laboratory tests done prior to blood transfusion demonstrated an unex- pected antibody. Her blood group was A,, CcDEe. The antibody was strongly reactive to any of a large number of group 0 and A cells at room temperature. It reacted best at lower temperature with cells suspended in saline, but did not agglutinate autologous red blood cells even at 5 C. It was barely reactive to group 0 and A cord blood at room temperature. The antibody was not inhibited by saliva from group 0 and A secretors.

Received for publication January 25, 1978; accepted February 27, 1978.

A phenotype i with anti-I was suspected. The sample was sent to Osaka Red Cross Blood Center where the detailed study was performed.

She appeared to be intellectually within normal limits and no tests for metabolic disorders were done. There was horizontal nystagmus on right gaze. Her visual acuity was 0.02/0.02. She had had visual difficulty since her infancy. Visual disturbance advanced and cataract was surgically treated when she was 22 years of age.

A family study was camed out (Fig. 1 and Table l ) , and a brother was found to be pheno- type i. He also had a similar visual disturbance including the history of surgical treatment of cataract. These two had no history of hemato- logic disorders and laboratory tests were unre- markable. Although the family members had no knowledge of consanguinity, they did not deny that the parents of the patients were cousins. Titration score for I antigen was not done to find Iint in the family.

Discussion

There were 16 individuals of phenotype i in nine fa mi lie^.'.^*'.^.^^.^^ Including our case from Matsumoto, there have been 18 i mem- bers in ten families. All cases are summarized in Table 2. Although there is a male domi- nance (6 women and 12 men), it has been known that the pattern of inheritance is not that of X-linked recessive characters. Potent anti-I was detectable by saline method at room temperature in each of the i persons. Consanguineous marriage was recorded in three families. However, all familes were unrelated.

Congenital cataract is classified into several subtypes, and is often associated with other ophthalmic abnormalities, for example, nystagmus as seen in our proposi- t ~ s . ~ However, the status of eye disorders associated with i has not been described in detail. The i siblings of our case underwent ophthalmic surgery many years ago and no

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Volume 19 166 Number 2 Transfusion March. 4pril 1979

Volume 19 Number 2 PHENOTYPE i AND CATARACT 167

Table 1. Blood Groups of Family Members

11-2 (m) A,, MNss, P,, CcDEe. 11-3' (f) A,, NNss, P,, CcDEe, 11-4 (m) Al, NNss, Po. CcDEe, 11-5 (f) Al, NNss, Pz, CCDEe, 11-6 (m) 0, NNss, Po, CcDEe, 111-1 (f) 0, NNss, PZr CCDEe. 111-2 (m) 0. MNss. Pt, CCDee. 1113 (m) 0, MNss, Pz, CcDEe, 111-4 (m) 0, NNss, Po, CCDee, 111-5 (f) AB, NNss, PI, CCDee,

Le(a-b+), Fy(a+b-), Di(a-), Jr(a+), i Le(a-b-), Fy(a+b-). Di(a-), Jr(a+), i Le(a-b+), Fy(a+b+), Di(a-), Jr(a+), I Le(a-b+), Fy(a+b+), Di(a-), Jr(a+), I Le(a-b-), Fy(a+b-), Di(a-), Jr(a+), I Le(a-b+), Fy(a+b-). Di(a-), Jr(a+). I Le(a-b-), Fy(a+b-), Di(a-), Jr(a+), I Le(a-b-), Fy(a+b+), Di(a-), Jr(a+), I Le(a-b+), Fy(a+b-), Di(a-), Jr(a+), I Le(a-b-), Fy(a+b+), Di(a-), Jr(a+), I

' Propositus.

record was obtainable. The situation was similar in the most of other cases. They are obviously hereditary cases. All of these 16 were suffering from poor vision due to con- genital cataract. Cataract was not found in any of I members of these eight families.

There were two isolated cases in Niigata (case #8)3 and Miyazaki (case #6).' They were probably hereditary cases, as I-nega- tive status associated with various condi- t i o n ~ ~ was eliminated. It is desirable to confirm Iint on any pedigree study, but it has never been examined in Japan. The i woman in Niigata3 had surgical treatment for congenital cataract in her childhood. The man in Miyazaki,' had neither cataract nor poor vision, though he was known to be color blind. This was the only i Japanese without congenital cataract.

The association of phenotype i with con-

FIG. I. Family mem- bers of propositus.

I

genital cataract was demonstrated in 17 of 18 i Japanese. None of the 45 I members of these ten families had congenital cataract. There is, so far, no case suggestive of recombination, and pleiotrophy can not be ruled out completely. If it is a case of linkage which it is more likely to be, it must be a very close one as proposed by Yamaguchier a1.I0 The high frequency of this association in Japanese, has not been reported from any other Phenotype i is extremely rare in Japanese as it is in other races. Congenital cataract is also rare in Japan and recessive cases are much more infrequent than dominant cases.s The coincidence of these two rare genes must be extraordinally rare. Thus, although these nine families were recorded to be unrelated for at least a few to several generations, it is not impos- sible to presume that they were related in the

1 .f" I

0 . I 0,I AB.1 nt nt

I11

0,I 0,I

0 0 without cataract exp expired nt not tested 1 proDositus

with cataract

168 OGATA ET AL. Transfunion h(.rrh-Apd 1979

Table 2. Summary of Nine Japanese Families with i Individuals'

Case 1 2 3 4 5 6 7 8 9 10

Native place of Osaka families

Consanguineous marriage +

Number of family membemtested 12

i member Number 2 Sex m m Bloodgroup B A

i i Anti-lat RTin d d

saline m. and titer n x8

Congenital cataract + +

Number 10 Congenital

cataract

I member

- References 1 0 , l l

Osaka

-

6

2 f m A A i i d d

n n

+ + 4

- 10

Osaka

-

3

2 f m B B i i d d

n n

+ + 1

- 10

Osaka

-

4

2 m m O A i i d d

n n

+ + 2

- 10

Miya- zaki

-

5

2 m f A A i i d d

n x4

+ + 3

- 7

Miya- Miya- zaki zaki

-

2

1 m A i d

X8

-

1

- 7

-

5

2 m m A A i i d d

x4 n

+ + 3

- 8

Niig- lsezaki Matsu- ata mot0

+ + -

7 9 10

1 2 2 f m f m f A B B A A i i i i i d d d d d

x32 x16 x 4 x0 x16

+ + + + + 6 7 8

d: demonstrable; n: not described.

remote ancestors. It is well known that the Japanese had been relatively isolated for a long period and are comparatively pure anthropologically. The possibility should be checked by the investigation of Mongolian people in other countries.

Acknowledgments We are greatly indebted to Mr. Tatsuno and his

associates in the Miyazaki Red Cross Blood Center, Miss Nagashima and her associates in the Blood Bank in University of Niigata Medical School Hospital, and Mr. Hara and his associates in the Chiba Red Cross Blood Center for the information of the cases. We are also grateful to Dr. Yabe, Dr. Tsuzuki and Prof. Hayashi in the University of Shinshu Medical School for their kind cooperation.

References I . Hara, S.. E. Kitahara, F. Takahisa, Y. Honda, and

H. Hashimoto: A pedigree of study of an i person. Presented at the Japanese Society of Blood Transfusion, 1977.

2. McGinniss. M. H.. P. J. Schmidt, and P. P. Carbone: Close association of I blood group and disease. Nature 202:606, 1964.

3. Nagashima. S.. K. Yamada. H. Kishi, K. Urakawa, K. Kojima, and H. Nakajima: A case of pheno- type i. Presented at the Japanese Society of Blood Transfusion, 1976.

4. Race, R. R., and R. Sanger: Blood Groups in Man, 6th ed. Oxford, Blackwell, 1975, p. 449.

5. Shoji. Y.: Practice of Ophthalmology, 6th ed. Tokyo, Kanehara, 1976 (in Japanese).

6. Signal. T., and P. B. Booth A New Zcaland family with i members. Vox Sang. M:391, 1976.

7. Tatsuno, M., M. Yoshida, S. Ikeda, and R. Nagano: On rare isemti-I. J. J a p . Soc. Blood Transfusion 21:27, 1974 (in Japanese).

8. - , M. Yoshida, S. Ikeda, R. Nagano, and Y. Wakamatsu: On rare bloodgroupi. Presented at Japanese Society of Blood Transfusion, Kushic Branch, 1977.

9. Wiener, A. S., L. J. Unger, L. Cohen, and J. Feldman: Type-specific cold auto-antibodies as a cause of acquired hemolytic anemia and hemolytic transfusion reactions: biologic test with bovine red cells. Ann. Intern. Med. 44: 221, 1956.

10. Yamaguchi, H.. Y. Okubo, and M. Tomita: A note on possible close linkage between the Ii blood locus and a congenital cataract locus. Roc. Japan Acad. 48:625, 1972.

11. - , Y. Okubo, T. Tomita, H. Yamano, and M. Tanaka: A rare i (I negative) phenotype blood found in Japanese families. Roc. Japan Acad. 46.889, 1970.

Hiroyuki Ogata, M.D.. Blood Bank Pathologist, Blood Bank Section, University of Shin-shu Medical School Hospital, 3-1-1 Asahi, Matsumoto, Nagano-ken, Japan.

Yasuto Okubo, M.T., Technical Director, Osaka Red Cross Blood Center, 2-4-34 Morinomiya, Joto-ku Osaka, Japan.

Taro Akabane. M.D.. Professor, Dcpartment of Pediatrics, Faculty of Medicine, Shin-shu University, Director, Blood Bank Section, University of Shin-shu Medical School Hospital, 3-1-1 Asahi. Matsumoto. Nagano-ken, Japan.