摘要:

AbstractHereditary multiple exostosis (EXT) is an autosomal dominant disorder in which the clinical hallmark is the growth of bony protuberances from long bones and which can cause a variety of orthopedic deformities. This study sought to further delineate the natural history of EXT. In addition, since previous studies have suggested that there are deviations from Mendelelian expectations in EXT, including incomplete penetrance and a skewed sex ratio, we attempted to confirm or refute these suggestions. Both portions of the study were carried out through retrospective review of 43 affected probands and 137 of their affected relatives. Data are presented concerning frequency and severity of complications of EXT including short stature, sequelae of exostoses, occurrence of malignant degeneration of exostoses, and problems in pregnancy and delivery of affected females. Only 2.8% of the total affected population had experienced exostosis‐related malignancy, an estimate which is considerably less than earlier reports would suggest. Penetrance was 100%. There was an excess of males within the entire affected population (104:76) and within identified probands (28:15). However, the male to female ratio was unskewed in nuclear families (probands, affected sibs, and parents). The excess of males appears to be related to males having more severe and more frequent complications of EXT than having any primary genetic origin. © 1995 Wiley‐Liss,

ISSN:0148-7299    

DOI:10.1002/ajmg.1320550113

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractAmong 6800 consecutive blood samples studied for clinical cytogenetic diagnosis, we identified 30 families in which one parent of the proband had a balanced reciprocal autosomal translocation (excluding Robertsonian rearrangements). Twentyeight of the 30 families had a malformed and/or mentally retarded proband: 19 with an unbalanced derived chromosome, 3 with abnormalities involving chromosomes other than those in the translocation, 5 with a “balanced” reciprocal translocation, and 1 with a normal karyotype. We hypothesize that the latter 6 affected probands with “balanced” karyotypes could be abnormal due to submicroscopic deletions and duplications as was originally suggested by Jacobs [1984]. Particularly in these 6 families, 83% of translocation breakpoints were associated with fragile sites, more than expected by chance (P<0.025). This supports the report of an association between fragile sites and constitutional chromosome breakpoints by Hecht and Hecht [1984]. To explain these findings, we propose that autosomal fragile sites are unstable areas which predispose to breaks and unequal crossing over near the fragile site breakpoints creating minute duplications and deletions. Consequently, newborn infants inheriting a seemingly “balanced” karyotype from a normal parent with a balanced reciprocal translocation may still be at an increased risk of being malformed and/or developmentally delayed because of submicroscopic chromosomal imbalances. © 1995 Wil

ISSN:0148-7299    

DOI:10.1002/ajmg.1320550114

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractA molecular investigation of 16 Bantu‐speaking Black XX true hermaphrodites was undertaken in an attempt to determine the cause of the disorder. Y‐specific sequences, including sequences mapping to the sexdetermining region of the Y, were shown to be absent from lymphocyte tissue of all 16 patients tested. Y chromosome sequences were also absent from the ovarian and testicular components of both ovotestes of a single XX true hermaphrodite, thus excluding gonadal mosaicism involving Y chromosome sequences. Since there is evidence for Xp genes involved in testis determination/differentiation, uniparental disomy of the X chromosome was investigated in 14 XXTH families. Uniparental disomy was excluded in 12 of the 14 families, and isodisomy was excluded in the remaining two cases. © 1995 Wiley‐Lis

ISSN:0148-7299    

DOI:10.1002/ajmg.1320550115

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractThe Meckel syndrome (MS) is an autosomal recessive disorder classically defined by the triad of occipital encephalocele, multicystic kidneys, and polydactyly. Here we describe 3 sibs with varying manifestations of MS. The propositus had isolated cystic renal disease. The other sibs were both prenatally diagnosed with renal disease, polydactyly, and the Dandy‐Walker malformation, an unusual central nervous system defect in MS. These findings are discussed in the context of the phenotypic expression of MS and the nosology of this disorder and the cerebro‐reno‐digital (Meckel‐like) syndromes. © 1995 Wiley

ISSN:0148-7299    

DOI:10.1002/ajmg.1320550116

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractA newborn boy with a large anterior fontanel, minor facial anomalies, postaxial polydactyly, patent ductus arteriosus, and developmental delay had trisomy of 7p due to an i(7p) and a concomitant t(2;7) (q37.3; q11.1). Significant enlargement of the fontanel is the most characteristic finding in most patients with duplications involving 7p15‐pter. Asynchrony in fore‐ and hindbrain and hemisphere formation leading to brain asymmetry and various defects in the posterior fossa are typical of infants with duplications of 7p11‐p12. A variety of heart defects has also been found in more than 50% of patients with duplication of 7p segments.Isochromosome formation accompanied by whole‐arm translocation, resulting in uniparental isodisomy for the involved segment, is an extremely rare cause leading to partial trisomies. Although it is not clear whether isochromosome formation precedes the whole‐arm translocation or follows it, the secondary rearrangement may have adaptive significance. © 1995 Wiley

ISSN:0148-7299    

DOI:10.1002/ajmg.1320550117

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractWe used specific mutation analysis to estimate the proportions of males and females with ornithine transcarbamylase (OTC) deficiency whose mutations occurred in the germ cells of one of the parents. The mutations were identified in the probands, and subsequently carrier testing was performed on their mothers and some of the grandmothers. Of 28 OTC deficient males, only 2 (7%) had sporadic mutations (95% CI, 0.6–18.5%), whereas of 15 OTC deficient females, 12 (80%) had sporadic mutations (95% CI, 63–99%) (P<0.001). Based on these results we estimated the male/female mutation rate ratio (ν/μ) in the OTC gene to be approximately 52. Assuming a fitness for males with OTC deficiency of 0 and the proportion of new female mutants at 0.80, the estimated fitness of heterozygous females is 0.4. Because of the difference in mutation rates between male and female germ cells, we suggest that 9/10 or higher, rather than the conventional 2/3 proportion, be applied when estimating prior risk of carrier status in a mother of one affected male. The prior risk of a mother of an affected female is much lower, approximately 2/10. © 1995 Wiley‐L

ISSN:0148-7299    

DOI:10.1002/ajmg.1320550118

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractZygosity testing of all multiple births allowed the identification of a subgroup of 42 monozygotic twin pairs who have dichorionic placentas, fused and separate. Perinatal outcomes of this group were compared with 110 pairs of monochorionic monozygotic twins and 148 pairs of dizygotic twins. Dichorionic monozygotic twins had the lowest incidence of preterm birth, perinatal mortality, and birth weight discordance.There was an excess of like‐sexed over unlike‐sexed pairs among the dizygotic twins. © 1995 Wiley‐Lis

ISSN:0148-7299    

DOI:10.1002/ajmg.1320550119

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractInterstitial deletions of the long arm of chromosome 4 are rare. Different breakpoints are involved. Only one of the patients had a very similar deletion to that of the present case. Both had low birth weight at term; weight, length and head circumference less than the third centile; epicanthic folds; apparently low‐set abnormal ears; broad nasal bridge; micrognathia; hypoplastic nails; delayed psychomotor development; and mild mental retardation. © 1995 Wiley‐Liss,

ISSN:0148-7299    

DOI:10.1002/ajmg.1320550120

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractWe have examined the expression of SRY mRNA in individual in vitro fertilized preimplantation human embryos; because of ethical constraints, these studies were confined to embryos with one and three pronuclei. Using a sensitive reverse transcriptase‐polymerase chain reaction (RTPCR) assay, we observed SRY mRNA at the one‐cell through the blastula stages but not in spermatozoa. These results indicate that the de novo transcription of this sex‐specific gene occurs at a developmental time considerably earlier than that of gonadal differentiation. Our results also indicate that in vitro fertilized embryos with one pronucleus are likely to be diploid. © 1995 Wiley‐L

ISSN:0148-7299    

DOI:10.1002/ajmg.1320550121

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractExtra structurally abnormal chromosomes (ESACs) are small supernumerary chromosomes often associated with developmental abnormalities and malformations. We present 50 probands with ESACs characterized by fluorescencein situhybridization using centromere‐specific probes and chromosome‐specific libraries. ESAC‐specific libraries were constructed by flow sorting and subsequent amplification by DOP‐PCR. Using such ESAC‐specific libraries we were able to outline the chromosome regions involved.Twenty‐three of the 50 ESACs were inverted duplications of chromosome 15 [inv dup(15)], including patients with normal phenotypes and others with similar clinical symptoms. These 2 groups differed in size and shape of the inv dup(15). Patients with a large inv dup(15), which included the Prader‐Willi region, had a high risk of abnormality, whereas patients with a small inv dup(15), not including the Prader‐Willi region, were normal. ESACs derived from chromosomes 13 or 21 appeared to have a low risk of abnormality, while one out of 3 patients with an ESAC derived from chromosome 14 had discrete symptoms. One out of 3 patients with an ESAC derived from chromosome 22 had severe anomalies, corresponding to some of the manifestations of the cat eye syndrome. Small extra ring chromosomes of autosomal origin and ESACs identified as i(12p) or i(18p) were all associated with a high risk of abnormality. © 1995

ISSN:0148-7299    

DOI:10.1002/ajmg.1320550122

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY