Search PubMed⌕ Search

Biomedical subjects

E Sujansky

Publications and source records attributed to E Sujansky.

At least 19 recordsLinked to original sources
PubMed2000

Deletion of a 5-cM region at chromosome 8p23 is associated with a spectrum of congenital heart defects.

BACKGROUND: Cytogenetic evidence suggests that the haploinsufficiency of > or =1 gene located in 8p23 behaves as a dominant mutation, impairing heart differentiation and leading to a wide spectrum of congenital heart defects (CHDs), including conotruncal lesions, atrial septal defects, atrioventricular canal defects, and pulmonary valve stenosis. An 8p heart-defect-critical region was delineated, and the zinc finger transcription factor GATA4 was considered a likely candidate for these defects. We narrowed this region and excluded a major role of GATA4 in these CHDs. METHODS AND RESULTS: We studied 12 patients (7 had CHD and 5 did not) with distal 8p deletions from 9 families by defining their chromosome rearrangements at the molecular level by fluorescent in situ hybridization and short-tandem repeat analysis. Subjects with 8p deletions distal to D8S1706, at approximately 10 cM from the 8p telomere, did not have CHD, whereas subjects with a deletion that included the more proximal region suffered from the spectrum of heart defects reported in patients with 8p distal deletions. The 5-cM critical region is flanked distally by D8S1706 and WI-8327, both at approximately 10 cM, and proximally by D8S1825, at 15 cM. Neither GATA4 nor angiopoietin-2 (ANGPT2; a gene in 8p23 involved in blood vessel formation) were found to be deleted in some of the critical patients. We also found that CHDs are not related to the parental origin of deletion. CONCLUSIONS: Haploinsufficiency for a gene between WI-8327 and D8S1825 is critical for heart development. A causal relationship does not seem to exist between GATA4 and ANGPT2 haploinsufficiency and CHDs.

Adolescent↗
PubMed2000

Cloning, sequencing, and analysis of inv8 chromosome breakpoints associated with recombinant 8 syndrome.

Rec8 syndrome (also known as "recombinant 8 syndrome" and "San Luis Valley syndrome") is a chromosomal disorder found in individuals of Hispanic descent with ancestry from the San Luis Valley of southern Colorado and northern New Mexico. Affected individuals typically have mental retardation, congenital heart defects, seizures, a characteristic facial appearance, and other manifestations. The recombinant chromosome is rec(8)dup(8q)inv(8)(p23.1q22.1), and is derived from a parental pericentric inversion, inv(8)(p23.1q22.1). Here we report on the cloning, sequencing, and characterization of the 8p23.1 and 8q22 breakpoints from the inversion 8 chromosome associated with Rec8 syndrome. Analysis of the breakpoint regions indicates that they are highly repetitive. Of 6 kb surrounding the 8p23.1 breakpoint, 75% consists of repetitive gene family members-including Alu, LINE, and LTR elements-and the inversion took place in a small single-copy region flanked by repetitive elements. Analysis of 3.7 kb surrounding the 8q22 breakpoint region reveals that it is 99% repetitive and contains multiple LTR elements, and that the 8q inversion site is within one of the LTR elements.

Abnormalities, Multiple↗
PubMed1996

Neurofibromatosis type 1 and pregnancy.

Neurofibromatosis Type 1 (NF-1) is an autosomal dominant condition which has markedly variable clinical expression, with manifestations ranging from mild cutaneous lesions to severe orthopedic complications and functional impairment. The current obstetrical literature indicates that women with NF-1 have increased complications associated with pregnancy. However, the majority of publications are case reports involving no more than 11 patients each, and are likely biased toward reporting on cases in which complications occurred. This study presents data on pregnancy outcome in 105 women with NF-1. The data were obtained from questionnaires completed by the study participants, and by review of their pregnancy and peripartum medical records. The 105 women had a total of 247 pregnancies, resulting in 182 live births, 44 first trimester spontaneous abortions, 21 elective terminations, and 2 ectopic pregnancies. There were two sets of twins. The cesarean section rate in our series (36%) was greater than the general population rate (9.1-23.5%). In 7 of these patients, the cesarean section was required because of maternal NF-1 complications. The study did not show the previously reported increased incidence of preeclampsia, preterm delivery, intrauterine growth restriction, pregnancy-induced hypertension, stillbirth, spontaneous abortion, or perinatal mortality. Sixty-four (60%) of the one hundred five women reported growth of new neurofibromas during pregnancy and fifty-five (52%) noted enlargement of existing neurofibromas. Nineteen women observed no changes in the size of their neurofibromas and no growth of new neurofibromas during pregnancy.

Cesarean Section↗
PubMed1995

Outcome of Sturge-Weber syndrome in 52 adults.

Sturge-Weber syndrome (SWS) is a neurocutaneous disorder characterized by cutaneous facial angioma, leptomeningeal angioma associated with seizures and other neurologic complications including mental retardation, and glaucoma. Only limited information about long-term outcome, including the societal integration of adult patients, is available in the literature. Data on 52 adults with SWS, ages 18-63 years, ascertained through the Sturge-Weber Foundation, were obtained via written questionnaires, telephone interviews, and reviews of medical records. The distribution of port-wine stains (cranial 98%, extracranial 52%) and the prevalences of glaucoma (60%), seizures (83%), neurologic deficit (65%), and other complications were established. The age of onset of glaucoma (0-41 years), the age of onset of seizures (0-23 years), and the correlation between the distribution of port-wine stains and the prevalence of seizures was identified. The relationship between the age of onset of seizures and seizure control was established. In those with and without seizures, the prevalences of developmental delay (43% vs. 0%), emotional and behavior problems (85% vs. 58%), special education requirements (71% vs. 0%), and employability (46% vs. 78%) were analyzed. Overall, 39% were financially self-sufficient, and 55% were or could be married. Ten participants produced 20 liveborn offspring; 17 were healthy, and tuberous sclerosis, a café-au-lait spot, and a "birthmark" were found in 1 child each. The results of this study can be used for genetic counseling in Sturge-Weber syndrome.

Adolescent↗
PubMed1995

Sturge-Weber syndrome: age of onset of seizures and glaucoma and the prognosis for affected children.

Data were obtained on 171 individuals with Sturge-Weber syndrome via questionnaire and medical records. The age of the study group ranged from 2 months to 59 years; the median was 8 years. In addition to the facial location of port-wine stains in the areas of the trigeminal dermatomes present in 170 patients, 45% also had extracranial port-wine stains over the torso and/or extremities, and 17% had other vascular or pigmentary lesions. Seizures were present in 80% of all patients (87% of those with bilateral and 71% of those with unilateral port-wine stains); in all but one case, seizures were associated with port-wine stains in V1 alone or V1 and V2 trigeminal dermatomes location. The age of onset of seizures ranged from birth to 23 years; 75% had onset of seizures before 1 year of age; these children had an 83% incidence of developmental and academic problems. Fifty-eight percent showed early developmental delay and required special education classes. The rate of retardation showed a decreasing tendency with increasing age of onset of seizures; of the children without seizures, only 6% had developmental delay and 11% required special education classes. Glaucoma was present in 48% of patients (67% unilateral and 33% bilateral). Of all patients with glaucoma, 92% had port-wine stains in both V1 and V2 dermatomes and 8% only in V1. The laterality of glaucoma did not correspond to the trigeminal distribution of the port-wine stains in all instances. Glaucoma was diagnosed during the 1st year of life in 61% and by 5 years in 72%; one patient did not have onset of symptoms until 38 years. The results of our data can serve as a guide for estimating relative risk figures for seizures, glaucoma, and mental retardation in children with Sturge-Weber syndrome.

Adolescent↗
PubMed1994

Bone dysplasias of infancy in the Vienna collection.

The Vienna Museum of Pathological Anatomy contains a vast collection of abnormal skeletons. We have appraised this material and attempted to establish firm diagnoses of specific genetic disorders in terms of modern syndromic concepts. A number of the skeletons in the museum are those of deceased neonates; in many instances it was impossible to reach a diagnosis on the basis of the outward appearance but radiographic investigations confirmed diagnoses including osteogenesis imperfecta type II, thanatophoric dysplasia, achondroplasia and achondrogenesis. The Vienna collection represents a priceless resource for the investigation of genetic skeletal disorders of this type.

Achondroplasia↗
PubMed1993

Genetic skeletal dysplasias in the Museum of Pathological Anatomy, Vienna.

Skeletal material in the Museum of Pathological Anatomy, Vienna, has been appraised in order to modify existing descriptive designations and to establish diagnoses of specific genetic disorders. In this way osseous material relating to classical genetic syndromes has been identified and will be available for further study. Among the skeletons of adults in the museum, the following genetic conditions could be diagnosed: achondroplasia, Marfan syndrome, cleidocranial dysostosis, and diaphyseal aclasia. In adult sisters with dwarfism and a rickety bone disorder, the final diagnosis was uncertain. Infantile bone dysplasias, genetic conditions involving the skull, and malformation syndromes which are all represented in the museum are currently being analyzed.

Achondroplasia↗
PubMed1993

Natural history of the recombinant (8) syndrome.

The recombinant 8[Rec(8)] syndrome [rec(8), (8qter-->8q22.1::8p23.1-->8qter] is due to a parental inv(8)(8pter-->8p23.1::8q22.1-->8p23.1::8q22+ ++.1-->8qter). All inv(8) parents we have studied were of Hispanic origin. The Rec(8) phenotype consists of a characteristic set of minor facial anomalies, cardiovascular and other major malformations, and moderate to severe mental retardation. The clinical phenotype is relatively consistent in all published cases; however the natural history of the condition has remained unknown. Retrospective and prospective information on 42 propositi, spanning a period from 5 days to 23 years, allowed us to define the natural history of this syndrome, tabulate the frequency and the evolution of phenotypic abnormalities, and share our experience with different therapeutic approaches.

Abnormalities, Multiple↗
PubMed1993

Pulmonary arteriovenous malformation in the newborn: a familial case.

Pulmonary arteriovenous malformation (PAVM) is a rare cause of cyanosis in the newborn with nine previously reported cases. Typical signs at presentation include cyanosis, murmur, and congestive heart failure. Abnormality on chest x-ray is common with cardiomegaly, oligemia, and focal pulmonary density. There is a male predominance, unlike older children and adults with PAVM. Familial cases of PAVM have been reported with Osler-Weber-Rendu syndrome. We report a familial case of PAVM presenting in the newborn.

Arteriovenous Malformations↗
PubMed1992

Familial inclusion body myositis: evidence for autosomal dominant inheritance.

We report a kindred manifesting clinical features and muscle biopsy findings of inclusion body myositis (IBM). In this family, multiple members were affected in two generations with direct male-to-male and female-to-male transmission. This is the first reported instance of autosomal dominant inheritance in IBM, which usually occurs sporadically or, rarely, may be transmitted as an autosomal recessive disorder.

Adult↗
PubMed1991

San Luis Valley recombinant chromosome 8 and tetralogy of Fallot: a review of chromosome 8 anomalies and congenital heart disease.

Tetralogy of Fallot, the most common cyanotic heart defect, has not been closely associated with a specific chromosome defect. The San Luis Valley Recombinant Chromosome 8 [SLV Rec(8)] syndrome is strongly associated with congenital heart disease, particularly tetralogy of Fallot. This article reviews SLV Rec(8) syndrome and other chromosome 8 aberrations to suggest locations for cardiogenic genes. SLV Rec(8) [rec(8),dup q,inv(8)(p23q22)] syndrome has been found in Hispanic families in the southwestern United States. Congenital heart disease is found in 93.3% of SLV Rec(8) individuals (n = 45), with tetralogy of Fallot constituting 40.5% of all lesions and conotruncal defects, 55.6%. These frequencies exceed the incidence of tetralogy of Fallot (10%) and conotruncal defects (20%) among all children with heart defects (P less than 0.003 for both). Review of patients with deletion 8p (n = 13) showed heart defects in 84.6% with 27.3% being conotruncal defects. Among duplication 8q patients (n = 20), 45% had heart defects with conotruncal defects constituting 44%. Neither group differed significantly from expected in its incidence of conotruncal defects. Among patients with mosaic trisomy 8 (n = 47), 12 had heart abnormalities including one conotruncal defect. Among 3 patients with other rec(8) chromosomes, one had a ventricular septal defect. The cause of heart defects in SLV Rec(8) cannot be assigned to either the deletion of 8p or the duplication of 8q. The lack of an association between other chromosome 8 abnormalities and tetralogy of Fallot suggests that genes at the SLV Rec(8) breakpoints or an interaction between genes on both arms of chromosome 8 are important.

Chromosome Aberrations↗
PubMed1990

Attitudes of at-risk and affected individuals regarding presymptomatic testing for autosomal dominant polycystic kidney disease.

One hundred forty-one individuals with autosomal dominant polycystic kidney disease (ADPKD) and 137 at-risk individuals from 107 kindreds answered a questionnaire to determine knowledge and attitudes about ADPKD and the use of gene linkage analysis for prenatal and postnatal presymptomatic diagnosis. Both groups of individuals displayed a high level of knowledge about the disease. Although 87% of affected individuals considered the recurrence risk of ADPKD high, only 11% of ADPKD did not have children for this reason after diagnosis. Ninety-seven percent of at-risk individuals would utilize gene testing for themselves. Eight-eight percent of ADPKD and 89% of at-risk individuals would test offspring (not significant, NS) and 65% of ADPKD and 50% of at-risk individuals between the ages of 18 and 40 would use prenatal testing (NS). Only 4% of ADPKD and 8% of at-risk individuals between the ages of 18 and 40 would terminate a pregnancy for ADPKD. A greater percentage would terminate a pregnancy for a serious medical problem. The factors influencing presymptomatic testing were analyzed. The data suggest that presymptomatic testing will not substantially modify incidence of ADPKD since it may only occasionally alter reproductive plans.

Adolescent↗
PubMed1988

Linkage heterogeneity of autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease has been shown to be closely linked to the alpha-hemoglobin complex on the short arm of chromosome 16. We describe a five-generation kindred, descendants of Sicilian immigrants, in which the disease occurs but without linkage to the alpha-hemoglobin complex. DNA probes were used in genetic-linkage studies on blood samples from 163 family members, of whom 71 were affected by or at risk for autosomal dominant polycystic kidney disease. Diagnoses were confirmed by ultrasound examination. In this family the frequency of recombination between the alpha-hemoglobin complex and the region previously shown to contain the mutation causing polycystic kidney disease exceeded 24 percent, indicating a mutation at a different locus. The clinical findings in this family were indistinguishable from those in other families with polycystic kidney disease. We conclude that there is a second gene for autosomal dominant polycystic kidney disease. This apparent heterogeneity means that prenatal and presymptomatic diagnosis must be approached with caution until a method is found to distinguish between the two forms of the disease.

Adolescent↗
PubMed1987

Genetic risk for recombinant 8 syndrome and the transmission rate of balanced inversion 8 in the Hispanic population of the southwestern United States.

A rec(8) dup(q) syndrome, secondary to a pericentric inversion--inv(8)(p23q22)--has been identified in 26 probands from Hispanic kindreds in the southwestern United States. The clinical phenotype of the Hispanic rec(8) syndrome includes a dysmorphic facies, cardiovascular and urinary-tract malformations, and mental retardation. Segregation analysis utilizing pedigree and cytogenetic data from 31 kindreds including five additional kindreds from additional sources has provided computation of genetic risks for counseling. An inv(8) carrier parent has a 6.2% risk of having a rec(8) child. The transmission rate of the inv(8) was significantly higher for inv(8) carrier mothers (59%) than for carrier fathers (42%). The combined transmission rate for both sexes was 53%. Risk for spontaneous abortion or stillbirth (11.3%) was not higher than the general population frequency of 13%-15%. It is significant that all kindreds identified to date are of Hispanic background with ancestors traced to the southern Colorado/northern New Mexico region. By means of extended pedigree information, three independently ascertained kindreds have been linked through common ancestry 4 generations in ascendance. The Hispanic background, geographic localization, and common ancestry in three kindreds suggest a single founder of the Hispanic inv(8) in the Southwest.

Chromosome Inversion↗
PubMed1985

Bloom's syndrome.

Explore the source record for details and available documents.

Bloom Syndrome↗
PubMed1984

Clinicopathologic and dysmorphic findings in recombinant chromosome 8 syndrome.

Clinical records, autopsy reports, and microscopic slides from 11 infants with the recombinant 8 syndrome, an inherited abnormality of chromosome 8 affecting Hispanics from New Mexico and Colorado, were evaluated. A prevalence of cardiac and genitourinary anomalies was found, while few central nervous system abnormalities were observed. Dysmorphic features associated with recombinant 8 syndrome are presented, with descriptions of the inheritance pattern and recurrence risk. Because recombinant 8 syndrome is a chromosomal disorder that will appear more and more frequently as kindreds enlarge, pathologists must be alert to its diagnostic characteristics and genetic implications.

Abnormalities, Multiple↗