THis study was initiated vjhen it was learned that renal disease had occurred frequently in a large kindred and had resulted in the death of several affected males. The members of the kindred were alarmed at its seriousness and welcomed an investigation. The disorder in this kindred appears to be chronic interstitial pyelonephritis but differs from that disorder as it occurs in the general population in that most of the females are mildly affected while the males develop progressive renal insufficiency. The data suggest that the females acquire the disease at an early age but recover in many instances. Females without clinical manifestations who have been regarded as possessing the abnormal trait have been identified as carriers when the disease has been observed in their children. A defect which seems in some way to be associated with the disease is a form of progressive nerve deafness. This has been observed in most of the affected males. Clinical and laboratory studies were made on 134 members of the kindred and are being reported in detail elsewhere (Perkoff et al., 1951). The present paper is concerned primarily with the inheritance of the trait and related problems.

Fourteen years ago interest was aroused in a single kindred show­ ing hereditary nerve deafness. Studies to try and establish the mode of inheritance, and the anatomic location of the lesions have been attempted during this period. It was hoped that this information might give a clue to the physiologic pathology of hereditary nerve disease, and perhaps yield an approach to its treatment. The Mormon community presents a unique opportunity for the study of hereditary disease. Since it is an agrarian population, which does not move from its farms, its members can be relatively easily located. Because of this, a gene may be followed from a single polygamous male through generations of a rapidly expanding population.

Psoriasis is a chronic inflammatory skin disorder of unknown etiology and inconstant course which constitutes about 6% of all new skin cases seen by dermatologists. 1 Of interest is the association of arthritis and psoriasis. This arthritis is characterized by absorptive phenomena usually of peripheral joints and has been considered to be a distinct form of joint disease. 2,3 The familial occurrence of psoriasis is well known and studies have described the inheritance as recessive, double recessive, and irregular dominant. Schamberg 4 reviewed 592 patients with psoriasis and reported a family occurrence of 13%. He concluded that there was no satisfactory evidence for genetic transmission of this disease. Steinberg et al. 5 examined 464 patients with psoriasis. The disease was present among the patient's siblings 4 times as often when one parent had psoriasis as when neither parent was affected. Six per cent of the patient's parents had psoriasis. Because

HEREDITARY MULTIPLE SEBACEOUS CYSTS Get access F. E. STEPHENS F. E. STEPHENS Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Heredity, Volume 50, Issue 6, November/December 1959, Pages 299–301, https://doi.org/10.1093/oxfordjournals.jhered.a106931 Published: 01 November 1959

CancerVolume 11, Issue 5 p. 967-972 ArticleFree Access A recheck of kindred 107, which has shown a high frequency of breast cancer F. E. Stephens Ph.D., F. E. Stephens Ph.D. Laboratory of Human Genetics, University of Utah, Salt Lake City, UtahSearch for more papers by this authorEldon J. Gardner Ph.D., Eldon J. Gardner Ph.D. Laboratory of Human Genetics, University of Utah, Salt Lake City, UtahSearch for more papers by this authorCharles M. Woolf Ph.D., Charles M. Woolf Ph.D. Laboratory of Human Genetics, University of Utah, Salt Lake City, UtahSearch for more papers by this author F. E. Stephens Ph.D., F. E. Stephens Ph.D. Laboratory of Human Genetics, University of Utah, Salt Lake City, UtahSearch for more papers by this authorEldon J. Gardner Ph.D., Eldon J. Gardner Ph.D. Laboratory of Human Genetics, University of Utah, Salt Lake City, UtahSearch for more papers by this authorCharles M. Woolf Ph.D., Charles M. Woolf Ph.D. Laboratory of Human Genetics, University of Utah, Salt Lake City, UtahSearch for more papers by this author First published: September/October 1958 https://doi.org/10.1002/1097-0142(195809/10)11:5<967::AID-CNCR2820110516>3.0.CO;2-OCitations: 11AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 Gardner, E. J., and Stephens, F. E.: Breast cancer in 1 family pup. Am. J. Human Genet. 2: 30–40. 1950. 2 Gardner, E. J., and Woolf, C. M.: Intestinal poly-posis and carcinoma originating from mutation in mily group. Cancer 5: 695–699. 1952. 3 Jacobsen, O.: Heredity in Breast Cancer; a Genetic and Clinical Study of Two Hundred Pmbands. Copen hagen, Denmark. Nyt Nordisk Forlag, Arnold Busck. 1946; p. 306. 4 Penrose, L. S.; MackenWe, H. J., and Karn, M. N.: Genetical study of human mammary cancer. Brit. J. Cancer 2: 168–176. 1948. 5 Woolf, C. M.: Investigations on genetic as of carcinoma of stomach and breast. Univ. Calfornia Publ., Pub. Health 2(4): 265–349. 1955. 6 Woolf, C. M., and Gardner, E. J.: Familial dis tribution of breast cancer in a Utah kindred. Cancer 4: 515–520. 1951. Citing Literature Volume11, Issue5September/October 1958Pages 967-972 ReferencesRelatedInformation

In 1951 we reported the genetically predictable occurrence of chronic renal disease with associated nerve deafness in a large family. 1,2 One hundred thirty-four members of the family were examined, and adequate clinical data were available concerning three of seven males in the family who had died of uremia in the recent or remote past. Of the 44 members involved, 43 had pyuria, 32 had hematuria, all had cylinduria, and for 17 of 32 studied, the urine cultures were positive for bacteria. Of 59 patients studied, 14 had abnormal audiograms. Five of those with hearing deficits showed no evidence of renal disease at the time of examination, but two of these were found to be carriers of the trait for renal disease in that the renal lesion was observed in their descendants. Microscopic sections from one postmortem examination showed severe, diffuse interstitial pyelonephritis with inflammatory infiltrate, microscopic abscesses, normal glomeruli,

INFORMATION ON THE FREQUENCY of consanguineous marriages in human populations in arriving determinations the breeding structure sub-lethal recessive generations restored be negatively correlated with the mean coefficient of inbreeding of the population. Therefore, equal, the genetic effects of an atomic bombing fewer generations in populations a high frequency of consanguineous marriages.

BORBERG, A., 1951. Clinical and genetic investigations into tuberous sclerosis and Reckling. hausen's neurofibromatosis. Opera ex Domo Biologiae Hereditariae Humanae Universitatis Hafniensis, V. 23, pp. 239. Copenhagen: E. Munksgaard. CROWE, F. W., AND SCHULL, W. J., 1953. Diagnostic importance of cafe au lait spot in neurofibromatosis. Arch. Int. Med., 91: 758-766. FALLS, H. F., AND NEEL, J. V., 1951. Genetics of retinoblastoma. Arch. Op/kth., 46: 367-389. NEEL, J. V., AND FALLS, H. F., 1951. The rate of mutation of the gene responsible for retinoblastoma in man. Science, 114: 419-422. PREISER, S. A., AND DAVENPORT, C. B., 1918. Multiple neurofibromatosis and its inheritance, with description of a case. Am. J. Med. Sci., 156: 507-540.

T HE problems of investigation of human inheritance are multiple and actually quite different from the problems that face an individual who would study inheritance in other forms, where controlled experimental observations can be made. We are, of course, limited in our primary material to the observation of what is happening under natural circumstances in human society. The study of human inheritance is limited not only by this fact, but also by the fact that we live essentially as long as the people whom we hope to study; therefore, in general, we are fortunate if we can observe more than one or two generations at a given cross section of time in which we make our studies, and as we shall see in discussing the problems which we face in the investigation of human inheritance, this becomes a very serious and sometimes quite critical problem in the evaluation of results. I want to discuss with you briefly the clinical problems which we meet in terms of recognition of a disease, its identity in all of its ramifications, and the useful purely clinical information that comes from genetic investigation. I shall describe three disease processes which we have studied in some detail here, and Dr. Stephens will then outline the conclusions we have made about these diseases from the genetic point of view as a result of our studies. In general, the investigation of human inheritance starts out with a so-called propositus; that is, a patient with a particular disease, which either because of the patient's knowledge of his family or because of previous clinical information about that disease, we presume to be genetic in character. The problem

Hereditary hemorrhagic telangiectasia is a vascular disease characterized by dilatation of arterioles, capillaries and venules into angiomata. These lesions are hereditary and the ectatic vessels frequently bleed spontaneously or after the slightest trauma. Although these lesions appear in all parts of the body, one of the most common sites is the oronasal cavity. Since nasal lesions are especially susceptible to injury, severe epistaxis frequently brings patients with this disease to the otolaryngologist. This offers him an opportunity to make a definitive diagnosis and to initiate studies to determine whether similar lesions exist elsewhere in the body.

1.1. Hereditary muscular diseases can best be studied in large family groups in which the variety of expressions of the same gene can be identified. Extending examinations by physicians to greater numbers of individuals in kindreds being studied will also add much to our understanding of these diseases and our knowledge of the pattern of their inheritance.2.2. Progressive muscular dystrophy is perhaps the most important and best known group of muscular disorders.3.3. Most cases of progressive muscular dystrophy can be classified into two general groups, the facioscapulohumeral type and the childhood type. Each of these is inherited as a separate genetic entity following a different pattern of inheritance.4.4. Facioscapulohumeral progressive muscular dystrophy varies in its form of expression. Its age of onset is usually between seven and twenty years. It is inherited as an autosomal dominant.5.5. Childhood progressive muscular dystrophy differs from facioscapulohumeral muscular dystrophy both in its mode of inheritance and in its pattern of expression. The age of onset is usually about three years. There is good evidence that it is inherited as a sex-linked recessive trait.6.6. The gene producing childhood muscular dystrophy has a high mutation rate. Its minimum mutation rate is roughly estimated at one in 10,000 (approximately 1 × 10−5).7.7. Three types of myotonia are discussed, myotonia congenita (Thomsen's Disease), paramyotonia and myotonia dystrophica.8.8. Myotonia congenita is not a common disease. It is congenital or can be identified at a very early age. It is inherited as an autosomal dominant.9.9. Paramyotonia is a rare disease. It is expressed as an immobility of the muscles brought on by cold. It can be detected when a child is but a few months old and is inherited as an autosomal dominant.10.10. Myotonia dystrophica is the most common as well as the most severe form of the myotonias. It is inherited as an autosomal dominant with a wide variability of expression.11.11. It is evident that all cases of family periodic paralysis described in the literature are not due to the same mutation. In the kindred studied at the University of Utah the defect was inherited as an autosomal dominant.12.12. Since the traits described as being due to autosomal dominant genes have not occurred in the homozygous condition it cannot be determined whether or not dominance is complete or what the expression of the homozygoteisTable II Statistical, Comparison of data on kindred with periodic paralysis with the theoretic behavior of a dominant trait∗PhenotypesObservedCalculatedDeviationStandard ErrorD/SENormal (pp)363424.12485Affected (Pp)32342Total6868∗From Tyler, Stephens, Gunn and Perkoff, J. Clin. Investigation, 1951.

THIS REPORT deals with a kindred in which many members are affected by a form of renal disease which has led to the death in uremia of several male members of the kindred and which is characterized by most of the manifestations of chronic interstitial pyelonephritis of the type reported by Weiss and Parker. 1 The high incidence of pyelonephritis in a single kindred offered an extraordinary opportunity to study both the clinical manifestations and the genetic background of the disease found in this group. The hereditary occurrence of any form of nephritis is distinctly unusual, and no reports of hereditary pyelonephritis have been found in the literature. Rinkoff and his co-workers, 2 in 1939, reported the occurrence of chronic glomerulonephritis in three brothers. They reviewed the literature as far back as 1875. The disease in their patients was characterized by hypertension, edema, and hematuria. In other reports many instances