摘要:

AbstractSex chromosome aneuploidy is the most common numerical chromosomal abnormality in humans at birth and a substantial portion of these abnormalities involve paternal chromosomes. An efficient method is presented for using air‐dried smears of human semen to detect the number of X and Y chromosomes in sperm chromatin using two‐chromosome fluorescence in situ hybridization. Air‐dried semen smears were pre‐treated with dithiothreitol and 3,4‐diio‐dosalicylate salt to decondense the sperm chromatin and then were hybridized with repetitive sequence DNA probes that had been generated by PCR and differentially labeled. Hybridizations with X and Y specific probes showed the expected ratio of 50%X:50%Y bearing sperm. Sperm carrying extra fluorescence domains representing disomy for the X or Y chromosomes occurred at frequencies of ∼4 per 10,000 sperm each. Cells carrying both X and Y fluorescence domains occurred at a frequency of ∼6/10,000. Thus, the overall frequency of sperm that carried an extra sex chromosome was 1.4/1,000. The frequencies of sperm carrying sex chromosome aneuploidies determined by hybridization did not differ statistically from those reported from the same laboratory using the human‐sperm/hamster‐egg cytogenetic technique. Multi‐chromosome fluorescence in situ hybridization to sperm is a promising method for assessing sex‐ratio alterations in human semen and for determining the fraction of sperm carrying sex or other chromosome aneuploidies which may be transmissible to offspring.

ISSN:0148-7299    

DOI:10.1002/ajmg.1320530102

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

年代:1994

数据来源: WILEY

摘要:

AbstractFourteen marker chromosomes were studied by FISH (fluorescence in‐situ hybridization) in cytogenetic preparations from 13 patients. The derived markers were identified as one isodicentric bisatellited mar(22), one fragment sized r(X), one fragment sized r(Y), one i(18p), small autosomal ring markers in three different patients derived from chromosomes 2, 8, and 8, a marker comprised of 9p and part of 9qh, and 3 bisatel‐ lited apparently monocentric markers; one of each from chromosomes 13 or 21, 14 or 22, and 15. Two fragment sized small ring markers in one patient and a small ring marker in another were negative with all twenty‐two different probes used. In addition, the small ring marker Y chromosome that was found in a boy with karyotype 46, X,−Y,+mar was negative with both pDXZ1 and pDYZ3. This anomaly of negative results with the battery of centromeric alphoid probes can be explained if one breakpoint for some small ring markers is very near to or within the centromere. Only some of the pericentromeric repetitive sequences in the normal chromosome would be represented in the chromosome specific alphoid probes, and presumably those corresponding to the currently available probes are truncated during the formation of the unidentified markers. In three of the small ring markers the FISH signal on the marker was much stronger than on the normal homologues in various proportions of cells, and this may indicate that some of the fragment sized small rings were multicentric. The literature was reviewed for Distamycin A/DAPI negative small ring markers that were present as extra chromosomes. There were only single published cases of most small rings but there were three r(8) cases, two r(l) cases, two r(12) cases, and two r(20) cases, uncomplicated by the presence of other chromosome abnormalities. Most cases with similar small rings were quite dissimilar phenotypically and syndrome identification was not possible, but in pooled data, 18/23 (about 80%) were developmentally and/or phenotypically abnormal. Some patients (5/23, about 20%) with small rings were dysmorphicwithoutintellectual handicap. Of 28 such patients with small ring markers (Distamycin/Dapi negative) in pooled data there are 6 (about 20%) with multiple markers mostly derived fromdifferentchromosomes. This is a very high figure and would suggest that the ring formation events, although involving different chromosomes, must be related and must be an indicator of the mechanism of origin of this group of markers. © 1994 Wiley

ISSN:0148-7299    

DOI:10.1002/ajmg.1320530103

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

年代:1994

数据来源: WILEY

摘要:

AbstractClinical assessments made with measuring devices are generally considered “objective” and “accurate” and are, therefore, more discriminating than subjective assessments. We show that the choice of measuring devices or non‐standardized landmarks to be used with the measuring devices affect the “accuracy” of the “objective” findings. © 19

ISSN:0148-7299    

DOI:10.1002/ajmg.1320530104

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

年代:1994

数据来源: WILEY

摘要:

AbstractWe report on a 31‐week fetus with hydrocephalus, hypertelorism, microtia, short neck, vertebral and rib defects, scoliosis, omphalocele, exstrophy of bladder, absent external genitalia and pubic rami, imperforate anus, diaphragmatic hernia, defective lobulation of lungs, single kidney, bicornuate uterus, and flexion deformities of the limbs. Similar extensive anomalies in the rostral and caudal regions were described by Russell et al. [Pediatrics, 67:176–182, 1981] and Stewart et al. [Am J Med Genet, 45:426–429, 1993]. The patients described by them had a combination of the oculo‐au‐riculo‐vertebral sequence (OAV) and caudal deficiency sequence, whereas the patient reported here can best be described as a combination of OAV and OEIS (omphalocele, exstrophy of bladder, imperforate anus, spinal defects) complexes. The widespread malformations seen in our patient may be the result of an error during blastogenesis. © 1994 Wil

ISSN:0148-7299    

DOI:10.1002/ajmg.1320530105

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

年代:1994

数据来源: WILEY

摘要:

AbstractWe report on a fetus with a de novo unbalanced translocation 3;10 and a microscopic neuroblastoma. The fetus had the kary‐otypic and phenotypic manifestations of partial dup (3q). The finding of a constitutional chromosomal abnormality and a microscopic neuroblastoma, although possibly coincidental, supports Knudson's two hit hypothesis for development of neuroblastomas and other embryonal tumors. In this case the first mutation is represented by the constitutional abnormality, possibly resulting in the microscopic neuroblastoma. A second mutation affecting the abnormal cells, which may be more prone to mutagenesis, may trigger a neuroblastoma. © 1994 Wiley‐Liss,

ISSN:0148-7299    

DOI:10.1002/ajmg.1320530106

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

年代:1994

数据来源: WILEY

摘要:

AbstractAnalysis of families with non‐syndromal split hand/split foot (SHSF) confirms the existence of 2 distinct entities, most probably caused by at least 2 different autosomal dominant genes. In the families in which the SHSF malformation is non‐syndromal and limited to the hands and feet (type I), the pattern of inheritance is of a regular autosomal dominant gene with a high penetrance (96%). In families in which at least one individual has other limb malformations and SHSF (type II), the transmission is often unusual. In most families, the gene is non‐penetrant, sometimes for generations, before the birth of the first affected individual. Thereafter, among the descendants of affected individuals, the penetrance is reduced (66%), suggesting the possible existence of another gene which controls the appearance of the clinical manifestations. The possibility that SHSF associated with other limb malformations is a disorder caused by trinucleotide repeat instability is raised. © 1994 Wiley‐L

ISSN:0148-7299    

DOI:10.1002/ajmg.1320530107

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

年代:1994

数据来源: WILEY

摘要:

AbstractWe report the familial occurrence of diaphragmatic agenesis in association with other midline anomalies in a brother and sister. Opitz and Gilbert [Am J Med Genet 1982, 12:443–455] introduced the concept of the midline as a developmental field, and there have been reports of pedigrees compatible with the hypothesis of an X‐linked gene regulating the development of the mid‐line. This family suggests that an autosomal gene also contributes to the morphogenesis of midline structures. © 1994 Wiley‐L

ISSN:0148-7299    

DOI:10.1002/ajmg.1320530108

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

年代:1994

数据来源: WILEY

摘要:

AbstractA 5‐month‐old girl with mild phenotypic abnormalities, developmental delay, and seizures was found to have the de novo kary‐otype 46,XX,−13,+der(13)t(X;13)(p21.2;p11.1). The partial trisomy of Xp21.2 → pter was confirmed with fluorescence in situ hybridization, using an X chromosome painting probe and several cosmid and YAC probes for Xp sequences. Replication banding showed that one of the structurally normal X chromosomes was late‐replicating, but that the Xp segment of the der(13) was early‐replicating in all cells examined. Since segments of the X chromosome separated from the X inactivation center in Xql3.2 cannot undergo X inactivation, the result is functional disomy of distal Xp. As the loss of short arm material from chromosome 13 is not considered to be clinically significant, the genomic imbalance of Xp expressed in this patient most likely accounts for her abnormal phenotype. © 1994 W

ISSN:0148-7299    

DOI:10.1002/ajmg.1320530109

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

年代:1994

数据来源: WILEY

摘要:

AbstractWe have studied 9 cases with the combination of some form of holoprosencephaly and any degree of caudal dysgenesis. The cases were identified through the Spanish Collaborative Study of Congenital Malformations (ECEMC). Of the 9 cases, 6 infants had an aneuploidy syndrome, one had Meckel syndrome, and 2 cases were of unknown etiology. We determined that the prevalence figure for the association of both conditions in the same child was 0.08 per 10,000 livebirths, and 18.8 times higher for stillbirths (i.e., 1.50/10,000). This prevalence is significantly higher than what would be expected by Chance. © 1994 Wiley‐Liss, I

ISSN:0148-7299    

DOI:10.1002/ajmg.1320530110

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

年代:1994

数据来源: WILEY

摘要:

AbstractWe report on twins of unlike sex who shared a 45, X/46, X, +mar karyotype. The mar chromosome was found to be Yq− by DNA analysis. Marker studies, including 8 VNTR loci, yielded a probability of monozygosity of 0.99999996. © 1994 Wiley‐Liss,

ISSN:0148-7299    

DOI:10.1002/ajmg.1320530111

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

年代:1994

数据来源: WILEY