Renata Laxova

The critical region on the human Xq

SummaryAdult female carriers of balanced X; autosome translocations (118 cases) and of balanced X inversions (31 cases) have been collected from the literature. Forty-five of the 118 translocation carriers in whom the break was in the critical region (Xq13–q22, Xq22–q26, separated by a narrow region within Xq22) showed gonadal dysgenesis. Seven of the 31 inversion carriers in whom the break was in the same region also had gonadal dysgenesis, whereas the remaining 24 were normal in this respect. The critical region consists mainly of Q-bright material, and is the fifth brightest segment in the human genome. The region contains relatively few genes. It is possible that meiotic crossing-over, rarely, if ever, takes place in it. The critical region may therefore consist of two “supergenes” whose integrity must be maintained to allow normal ovarian development. The effect exerted by this region differs from other known position effects, in that it is independent of the break-point within the region and of the chromosome bands to which the broken ends are attached. One possible mechanism causing this effect might be a change in the replication order of the chromosome bands, which, in turn, might affect their function.

Del(10)(q22.3q24,1) associated with juvenile polyposis

Juvenile polyps are the most frequent gastrointestinal polyps with a malignant potential for which the genetic basis is unknown. Juvenile polyps, with a normal epithelium but hypertrophic lamina propria, are histologically quite distinct from adenomatous polyps which have dysplastic changes in epithelial nuclei. Furthermore, the adenomatous polyposis coli (APC) gene on Chr 5, mutated somatically in adenomatous polyps and mutated in the germline of patients with familial adenomatous polyposis, is not linked to hereditary juvenile polyposis. We provide the first report indicating that a tumor suppressor gene associated with juvenile polyposis may be located at 10q22.3q24.1. Cytogenetic studies of a patient with juvenile polyposis and multiple congenital abnormalities of the head, extremities, and abdomen revealed a de novo interstitial deletion of Chr 10 as the only defect, del(10)(10q22.3q24.1).

Amylase heterogeneity variants in man

The existence of six amylase heterogeneity variants in serum and urine has been discovered in a group of 111 families with twins, and the frequence of each variant was determined. It had been shown that each of these amylase heterogeneity variants is inherited codominantly, and the mode of inheritance is demonstrated schematically.These amylase heterogeneity variants may be used as an aid to twin zygosity determination and also in paternity problems.

Familial ovarian germ cell cancer: Report and review

Ovarian germ cell cancers are rare malignancies accounting for less than 5% of all ovarian cancers. We present a family in which three closely related women were diagnosed with ovarian germ cell malignancies. This familys cancer history prompted a family history investigation of women treated for ovarian germ cell malignancies in the Gynecologic-Oncology Clinic at the University of Wisconsin. One of the eight patients whose family histories were reviewed had an uncle who had been diagnosed with testicular germ cell cancer. A review found six other previously reported families in which more than one relative had been diagnosed with a malignant ovarian germ cell tumor. Additionally, several cases of families with both males and females diagnosed with germ cell cancers have been documented. The low incidence of ovarian germ cell cancers suggests that multiple occurrences in the same family may not be due to chance. Rather, it is possible that a gene conferring susceptibility to ovarian germ cell cancers, and possibly to germ cell tumors in males as well, is present in at least some of these families.

Congenital generalized fibromatosis. Case report and literature review.

A typical case of congenital generalized fibromatosis (CGF) is presented and the literature on this entity is reviewed. CGF is a rare condition which is probably heritable. It is manifested in infancy. Because of the unusual biological behavior of the fibromata, two clinical courses occur-death, if vital viscera are involved, or regression of the lesions and survival without significant disability. Including the present example, 63 cases have been reported.

Genitourinary abnormalities associated with the Smith-Lemli-Opitz syndrome.

The Smith-Lemli-Opitz syndrome is characterized by mental retardation, hypotonia, facial dysmorphism and abnormalities of the limbs, genitalia and kidneys. Since the latter 2 features have not been emphasized in the urological literature, the experience from the institution at which the syndrome was first described is reviewed and an illustrative case is reported. Upper urinary tract abnormalities were noted in 57 per cent and genital abnormalities in 71 per cent of the children evaluated.

Integrating genetic services into public health--guidance for state and territorial programs from the National Newborn Screening and Genetics Resource Center (NNSGRC).

aDepartment of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, Tex., bDepartment of Pediatrics and Medical Genetics, University of Wisconsin, Madison, Wisc., cMaternal and Child Health Bureau, Health Resources and Services Administration, Rockville, Md., dDepartment of Pediatrics, UCLA School of Medicine, Los Angeles, Calif., eCenter for the Society, the Individual and Genetics, UCLA, Los Angeles, Calif., fNational Newborn Screening and Genetics Resource Center, Austin, Tex., USA

Atelosteogenesis type III: Long term survival, prenatal diagnosis, and evidence for dominant transmission

We describe two additional instances of atelosteogenesis, type III, in a woman and her son. Clinical and radiographic information concerning these individuals allows further definition of this rare skeletal dysplasia. This is the first documentation of survival to adulthood of an individual with this disorder, of prenatal diagnostic assessment of an affected individual, and of vertical transmission suggestive of autosomal dominant inheritance. The clinical and radiologic phenotype of atelosteogenesis, type III overlaps with that of another skeletal dysplasia, autosomal dominant Larsen syndrome; these most likely represent allelic conditions.

Progress of a Comprehensive Familial Cancer Genetic Counseling Program in the Era of BRCA1 and BRCA2.

BRCA1 and BRCA2 mutation carriers have an increased risk of developing breast and/or ovarian cancer. Technical advances in genetic testing have increased the need for genetic counseling services; therefore, we have developed a counseling program for these individuals. The purpose of this study is to characterize this population, assess level of interest in genetic testing, and evaluate our program over a 5-year period. Our Familial Cancer Genetic Counseling Program was established in November, 1994. Information was collected prospectively, with comprehensive evaluation including complete pedigree, risk assessment, and counseling by a genetic counselor, geneticist, and oncologist. Data were collected on risk level, and subsequent recommendations for screening and/or genetic testing. There were 824 contacts recorded from November, 1994, through August, 1999. To date, 162 families have undergone comprehensive genetic evaluation and counseling. 90 (56%) were seen for a concerning family history and 72 (44%) were seen due to a personal history of malignancy. The majority of families had a significant level of risk with 126 (78%) families having two and 70 (43%) families having three affected first-degree relatives. Of the 162 families who received full counseling, 125 (77%) met criteria to recommend BRCA1/BRCA2 genetic testing. At this time, 30 of the 162 (18%) have had genetic testing. A brief phone contact or clinic visit is useful to screen individuals so that counseling can be directed toward truly high-risk families. In our program, the majority of families counseled were eligible for BRCA1/BRCA2 testing, but only 18% have elected to proceed at this time.

A Case of Translocation D--, t(lp÷)

SummaryA severely retarded, dystrophic, hypotonic boy with joint hyperflexibility, jaw anomalies, cerebral hypoplasia and failure to thrive is reported. He died at the age of 8 months. Clinical and biochemical investigation revealed predominantly normal values. An unusual type of palmar crease was found. Chromosomal studies showed a translocation, probably a mosaic with normal cells. The parents are chromosomally normal.