Identification by molecular diagnosis of mosaic Turner''s syndrome in an obligate carrier female for fragile X syndrome.

A case of mosaic Turner's syndrome with a 45,X/46,XX/47,XXX karyotype, who was also a fragile X obligate carrier as the mother of an affected boy, was identified by molecular diagnosis. Complete haplotyping and direct DNA analysis showed that the X chromosome in all metaphases was the normal X. At the age of 57, she is mentally normal. Her external appearance was typical of Turner's syndrome. This report shows that molecular studies in conjunction with cytogenetic analysis can help in the clinical diagnosis of a rare case and can show the uniqueness of a case such as the one here described.     

Triple X female and Turner''s syndrome offspring.

A mentally retarded young female having 47 chromosomes with a triple X karotype produced a child with Turner's syndrome associated with mental defeciency. To our knowledge this is the first example of a triple X female giving birth to a child with Turner's syndrome.     

Bone demineralisation in patients with Turner''s syndrome.

The hypothesis that the demineralisation associated with gonadal dysgenesis is analogous to post-menopausal osteoporosis was investigated. Bone mineral content of the distal forearm was measured in 11 adult patients with Turner's syndrome aged 18 to 57 years. As a group these patients were significantly demineralised (p less than 0.001) when compared with normal subjects. A bimodal distribution of bone mineral was demonstrated, the eight patients below the normal range having a bone mineral content 73% of normal. This may be the usual bone mineral content for a large proportion of Turner's patients. No steady reduction in mineralisation with age was demonstrated. The number of osteoporotic type fractures was obtained from the records of 36 adult patients with Turner's syndrome. From the cumulative total years at risk (770 patient years) from the age of 15 years, it was found that the number of fractures of the distal radius corresponded to the normal premenopausal rather than post-menopausal fracture incidence. The absence of any reduction in bone mineral content with age and no clear evidence of an increase in frequency of fractures both suggest that the demineralisation associated with Turner's syndrome is not analogous to post-menopausal osteoporosis. The regular use of long term oestrogen therapy as a treatment for 'osteoporosis' in these patients is therefore not justified.     

The neck in the XO and XX/XO mosaic Turner''s syndrome

An attempt to document both the clinical appearance of the neck and the roentgenographic findings of the cervical vertebrae in 15 cytogenetically diagnosed cases of the Turner syndrome rcvealed the following findings: 11 had webbed necks, 13 patients had short necks, and of those, 10 had a short and webbed neck. Fourteen patients had a low hairline, of those, three had a short neck and a low hairline. Ten patients had a webbed and a short neck with a low hairline.
Twelve patients had hypoplastic cervical vertebrae, of whom eight showed hypoplasia of all the cervical vertebrae and four showed hypoplasia of one or more cervical vertebrae.     

Detection of micro mutation in dystrophin gene of DMD female carrier

We attempted to identify a mutation in dystrophin gene in a female patient who was suspected a Duchenne muscular dystrophy (DMD) carrier with muscle weakness of upper limbs and congestive heart failure. We examined the mutation hot spots in DMD gene, exon 3, 6, 8, 13, 17, 19, 43, 44, 45, 47, 48, 49, 50, 52, 60 by multiplex PCR which had been a diagnostic screening strategy, and detected an extra band in exon 43 product. We also detected an extra band in exon 43 products by SSCP analysis for detection of small mutations which could not be detected by multiplex PCR. As a result of sequencing a PCR product of an exon 43, we confirmed an allele having the insertion of a 2 base of AT in Intron42, which is described for the first time. Although we can not conclude that this insertion is responsible for DMD, but it may cause abnormal splicing. In carrier detection of DMD without genetic information of proband, it is difficult to detect mutations by multiplex PCR solely. Therefore, SSCP of PCR products are recommended to detect mutation in DMD carrier.     

DMD基因内微卫星标记对女性携带者的诊断意义

目的对1临床诊断为Duchenne肌营养不良家系中两名女性个体进行连锁分析,以确定她们是否为Duchenne肌营养不良致病基因携带者。方法抽取家系成员外周血并提取基因组DNA,选取3个DMD基因内微卫星标记作引物进行PCR扩增,扩增产物经ABI PRISM377测序仪电泳后进行连锁分析。结果在我们所研究的Duchenne肌营养不良家系中,一女性个体为Duchenne肌营养不良致病基因携带者,而另一女性个体为正常基因型。结论基因内标记可以排除染色体交换,运用DMD基因内微卫星标记可以成功诊断Duchenne肌营养不良家系中女性个体是否为致病基因携带者。     

Molecular diagnosis of Turner''s syndrome.

Turner's syndrome is a common disorder which occurs in around 1/3000 live births in girls. Diagnostic use of polymorphic DNA markers for the X chromosome could help to reduce the number of time consuming karyotype analyses needed. The M27 beta probe maps on the X chromosome to Xcen-Xp11-22 and in 83% of female subjects detects heterozygosity with multiallelic polymorphism. In Southern blotting, a single X chromosome yields a single hybridisation band. In this study, genomic DNA was extracted from leucocytes of 49 patients with Turner's syndrome (karyotypes: 45,XO, n = 29; 45,XO/46,XX, n = 4; 46,Xi(Xq), n = 1; 45,XO/46,Xi(Xq), n = 4; 45,XO/46,Xr(X), n = 4; 45,XO/46,XY, n = 4; 46,XXp-, n = 3), digested with EcoRI or HindIII, and analysed by Southern blotting. The molecular data for each patient were compared with DNA controls (homozygous 46,XX, heterozygous 46,XX and 46,XY DNA). A single band of reduced intensity compared to homozygous 46,XX control DNA was seen in 41 cases. Two hybridisation bands of different intensities were seen in four patients, in one of whom mosaicism was suspected on the basis of molecular analysis, despite a 45,XO karyotype. In four cases, Turner's syndrome failed to be detected: one 45,XO/46,XX mosaicism with only 4% of 45,XO cells and three distal Xp deletions. DNA analysis appears to be a useful and rapid tool in screening for Turner's syndrome and could be an alternative to cytogenetic analysis in diagnosing the disorder when severe growth retardation or delayed puberty are not accompanied by a Turner phenotype.     

特纳综合征的心血管异常

目的 分析遗传性疾病特纳综合征(TS)合并的先天性心血管异常.方法 回顾25例女性TS患者临床特点及先天性心血管异常类型,并分析各种异常在不同核型患者中的分布情况.结果 40%TS患者合并先天性心血管异常,包括主动脉二叶瓣畸形、二尖瓣/主动脉瓣冗长或脱垂、冠状静脉窦扩张、房室增大及心肌致密化不全.45,XO型患者先天性...     

Follicular lymphoma in a X-linked lymphoproliferative syndrome carrier female

X-linked lymphoproliferative (XLP) syndrome is a rare primary immune-deficiency disorder caused by mutations of the SH2D1A or XIAP genes. Males with the disorder are usually in good health until contracting Epstein–Barr virus (EBV) whereupon the majority of patients die from fulminant infectious mononucleosis, lymphoma or hypogammaglobulinaemia. This report describes a female carrier with an XLP phenotype who was retrospectively identified after her grandson died from the disorder. Subsequent genetic testing identified the patient's mother and affected maternal grandmother as XLP carriers. The family's medical records were significant. The proband had lymphoma at ages 2 and 8 and made a full recovery following treatment. Both the maternal grandmother and uncle died of non-Hodgkin's lymphoma. We were concerned that the XLP carrier mother may be predisposed to lymphoma if the normal X chromosome is skewed towards inactivation. The human androgen receptor assay detected random X chromosome inactivation in the carrier mother. EBV was not detected in the lymphoma tissues of the proband and his grandmother, confirming previous findings that EBV is not always associated with lymphoma in XLP. More significantly, our study highlights the importance of identifying XLP in families with a high incidence of lymphoma.     

Dissection of the aorta in Turner''s syndrome.

Three deaths from dissection of the aorta in a series of 157 adult women with Turner's syndrome are reported. These are greatly in excess of the numbers expected. None of the three patients had a coarctation of the aorta. One had aortic regurgitation but there was no reason to believe that the aorta in the other two patients had been subjected to unusual haemodynamic stresses. Cystic medial necrosis of the aorta was described in two patients on whom necropsies were carried out. It is concluded that there is probably a greatly increased risk of dissection of the aorta in Turner's syndrome even in the absence of any other abnormality of the aorta and aortic valve. Previously reported cases of aortic dissection in Turner's syndrome are discussed.     

Cytogenetic and molecular findings in patients with Turner''s syndrome stigmata.

Cytogenetic and DNA analysis in 12 people with stigmata of Turner's syndrome was carried out. Cytogenetic analysis of these patients showed two subjects with 46,X, i(Xq) karyotypes, one with 45,X/46,X, i(Xq), one with 46,X,t(X;Y), and eight with 45,X/46,X,mar. Molecular analysis of DNA samples was performed in nine out of 12 patients with marker chromosomes. PCR analysis with oligoprimers specific for SRY, DYZ1, or DYZ3 loci identified Y chromosome material in five patients in the latter group. The X chromosome origin of the marker chromosome was proved by FISH technique with biotin labelled pericentromeric X chromosome specific probe in four other patients. These results show that patients with a number of Turner's syndrome stigmata usually do not have a typical XO karyotype but have some structural chromosomal aberrations involving the X or Y chromosomes. Combined application of cytogenetic, molecular cytogenetic (FISH), and PCR techniques significantly improves the precision of marker chromosome identification and thus might be of practical importance for the proper management and treatment of affected patients. Peculiarities of pathological manifestations of different karyotypes bearing structural abnormalities of the X or Y chromosomes in patients with Turner's syndrome stigmata, as well as feasible genetic mechanisms of sex determination and differentiation abnormalities in these subjects, are briefly discussed.     

Partial anomalous pulmonary venous drainage in two patients with Turner''s syndrome.

We report two cases of partial anomalous pulmonary venous drainage in a series of 135 patients with Turner's syndrome.     

An isolated case of Duchenne muscular dystrophy (DMD) in a female with a deletion of DMD cDNA

An isolated case of Duchenne muscular dystrophy (DMD) in a female who has a deletion of the DMD locus is described. This patient was a 26-year-old woman born to unrelated, healthy parents. She was initially examined at age 6 because of a waddling gait. At age 15, pseudohypertrophy of calves and pes equinus were observed along with proximal muscular weakness and wasting. Her serum creatine kinase level was high and histological evidence of muscular dystrophy was apparent on muscle biopsy. The patient was ambulant at age 15 and progression of motor disability has been slow. Chromosomal studies revealed a normal karyotype, and mental retardation is moderate. DNA analysis at age 26 revealed that she has a deletion of DMD cDNA 8 mapped within Xp21 and is heterozygous for the deletion. Since diagnosis of DMD is now dependent on the evidence of mutation or deletion at Xp21, this patient is thought to have a form of DMD. Expression of the DMD gene in the heterozygous state might be due to random but unequal lyonization.     

Parental origin of the X chromosome in a patient with a Robertsonian translocation and Turner''s syndrome.

We report on a proband with both a Robertsonian translocation and Turner's syndrome. Study of the parental origin of the X chromosome performed by microsatellite analysis indicates paternal origin of the X chromosome (Xpat). The occurrence of chromosome aberrations as a consequence of interchromosomal interactions is discussed.     

45,X Turner''s syndrome in monozygotic twin sisters.

A 7-year-old girl was admitted to the hospital for anaemia, secondary to intestinal blood los (melaena). She was found to have 45,X Turner's syndrome. Her identical twin sister also had Turner's syndrome with a 45,X chromosome complement. According to various criteria the probability of monozygosity was 0.9905. Although the incidence of twinning is greater than usual in families of patients with Turner's syndrome, affected cases have only been observed in twin sisters on six occasions. It seems therefore that the 45,X chromosome complement itself is not a factor predisposing to twinning, but that in some families, a factor is at play, which cuases either twinning or the 45,X aneuploidy, or both.     

The value of deletion analysis for carrier detection in Duchenne muscular dystrophy (DMD)

We performed genetic analysis for carrier detection for several at-risk females in a four-generation Duchenne muscular dystrophy (DMD) pedigree using deletion analysis. We demonstrated that dosage analysis is a suitable alternative method to determine the carrier status of female relatives of DMD patients shown to have a deletion within the DMD gene. Subsequently, we diagnosed an affected male fetus for an at-risk female shown to be a DMD carrier by deletion analysis. The usefulness of deletion and linkage analysis are compared. In this family, linkage analysis was complicated by the unavailability of key family members, two recombination events and by previously undisclosed nonpaternity. We found that dosage analysis was more efficient than linkage for carrier evaluation in this family.