Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since some patients with Ullrich-Turner syndrome (UTS) have mental retardation, we reviewed our experience to look for a high-risk subgroup. Among 190 UTS and gonadal dysgenesis patients with X chromosome abnormalities, 12 had mental retardation. All of the six (100%) with a small ring X were educable (EMI) or trainable mentally impaired (TMI) with more severe delay than expected in UTS. Among the 184 with other X abnormalities, only 6 had similar delays (2 from postnatal catastrophes), for a frequency of 3.3% mental retardation among those without a small ring X; only 2.2% of these had unexplained mental retardation. Polymerase chain reaction studies showed no Y-derived material in the 2 patients who were evaluated, and in situ hybridization confirmed X origin of the ring in the 6 subjects who were evaluated. We describe the phenotype of the 6 individuals with a small ring X, and an additional 2 patients with a small ring X who were identified outside the survey. The subjects with a small ring X comprised a clinically distinct subgroup which had EMI/TMI and shorter stature than expected in UTS. Seizures and a head circumference less than 10th centile were observed in half of the patients with a small ring X, and strabismus, epicanthus, and single palmar creases were present in more than half. A "triangular" face in childhood, pigmentary dysplasia, sacral dimple, and heart defects were also common. Neck webbing appeared to be less frequent than in 45,X. We hypothesize that the high risk of mental retardation in this form of the UTS results from lack of lyonization of the ring X due to loss of the X inactivation center. Excluding those with a small ring X, mental retardation is not significantly increased in patients with UTS.
 ...
PMID:Ullrich-Turner syndrome with a small ring X chromosome and presence of mental retardation. 141 51

We reviewed 122 cases of balanced X-autosome translocations in females, with respect to the X inactivation pattern, the position of the X break point and the resulting phenotype. In 77% of the patients the translocated X chromosome was early replicating in all cells analysed. The break points in these cases were distributed all along the X chromosome. Most of these patients were either phenotypically normal or had gonadal dysgenesis, some had single gene disorders, and less than 9% had multiple congenital anomalies and/or mental retardation. In the remaining 23% of the cases the translocated X chromosome was late replicating in a proportion of cells. In these cells only one of the translocation products was reported to replicate late, while the remaining portion of the X chromosome showed the same replication pattern as the homologous part of the active, structurally normal X chromosome. The analysis of DNA methylation in one of these cases confirmed noninactivation of the translocated segment. Consequently, these cells were functionally disomic for a part of the X chromosome. The presence of disomic cells was highly prevalent in translocations with break points at Xp22 and Xq28, even though spreading of X inactivation onto the adjacent autosomal segment was noted in most of these cases. This suggests that selection against cells with a late replicating translocated X is driven predominantly by a functional disomy X, and that the efficiency of this process depends primarily on the position of the X break point, and hence the size of the noninactivated region.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Functional disomies of the X chromosome influence the cell selection and hence the X inactivation pattern in females with balanced X-autosome translocations: a review of 122 cases. 173 64

Using reverse genetics, a candidate for the sex determining gene from the Y chromosome has recently been cloned. We have used a DNA probe from this gene to assess the presence of this crucial region of the Y chromosome in patients with sexual ambiguity or gonadal dysgenesis. The DNA from 3 cases of gonadal dysgenesis, one complicated by somatic anomalies and mental retardation, reacted normally with this putative sex determining gene. A patient having a small phallus and pseudovaginal, perineoscrotal hypospadias (PPSH) also had normal Y chromosomal DNA. We hypothesize that the defect in sex determination in all 4 cases is most probably subsequent to the primary sex determining switch.
 ...
PMID:Use of a probe for the putative sex determining gene, zinc finger Y, in the study of patients with ambiguous genitalia and XY gonadal dysgenesis. 236 11

An unbalanced translocation resulting in an unusually large partial 5q trisomy (5q11-5qter) and partial Xp monosomy (Xp11-Xpter) is reported in a 24 yr old woman with phenotypic abnormalities including gonadal dysgenesis and mental retardation. The karyotypes of the parents and the brother were found normal. Peripheral blood stimulated lymphocytes and cutaneous fibroblasts of the proband exhibited constantly, after BrdU incorporation, selective inactivation of the derivative X;5 chromosome spreading to the 5q duplicate segment. A variety of numerical and structural changes involving the derivative chromosome were observed in about 10% of cells of the cultured lymphoblastoid line established from the subject's lymphocytes. The extended 5q duplication, according to the literature, is generally accompanied by a severe phenotype and by developmental failure; it is therefore believe that genetic inactivation of the 5q duplicated region permitted the proband's development to adult age, despite the profound chromosomal imbalance.
 ...
PMID:An unusually large 5q duplication in an adult female subject: spreading of inactivation and in vitro instability of the derivative Xp/5q chromosome. 261 Apr 90

An abnormal extra band on the short arm of the X chromosome was found in a 7-year-old reared as a female, of mixed gonadal dysgenesis. She had ambiguous external genitalia, scoliosis, short stature, mental retardation and motor paralysis of the limbs. Chromosomal analysis revealed the karyotype of 46,Xp+ Y. An uterus with fallopian tube, a streak gonad on the left side and a testicle on the right side were discovered at exploratory laparotomy. Bilateral gonads and fallopian tube were removed. The chromosomal analysis of her normal mother showed the presence of the same abnormal X chromosome (46, X Xp+). In the literature, we found some cases of intersexuality with Xp+ in karyotype. The relationship between our own case and these Xp+ cases was discussed briefly. Thirty-five cases of mixed gonadal dysgenesis have been reported in Japanese literature, our own case being the 36th case.
 ...
PMID:[A case of mixed gonadal dysgenesis with structural abnormalities of X chromosome (Xp+)]. 406 Dec 20

Cytogenetic studies were done on a 5-year-old female with multiple congenital anomalies and mental retardation, revealing an unbalanced X/11 translocation. Her mother and phenotypically normal sister carry the balanced form of the translocation, while her brother has a normal 46,XY karyotype. Banding studies showed the breakpoints to be Xq22 and 11q13. These are remarkable for the following reasons: (1) the X breakpoint is within the critical region of the X chromosome, yet the balanced carrier does not manifest gonadal dysgenesis; and (2) the proband was trisomic for most of the long arm of chromosome 11. Late-replication studies of cells from the two balanced carriers showed inactivation of the normal X.
 ...
PMID:A possible exception to the critical region hypothesis. 746 94

We report cytogenetic and molecular investigations performed in two cases of mosaic trisomy 8 combined with mosaic sex chromosome aneuploidy. In a 35-year-old female, presenting with short stature, gonadal dysgenesis, and a multiple congenital anomalies/mental retardation syndrome typical of trisomy 8, chromosome analysis from peripheral lymphocytes showed the presence of three cell lines, whose karyotypes were 45,X (59.2%), 46,X,+8 (1.2%), and 47,XX,+8 (39.6%), respectively. The same cell lines were found in a skin fibroblast culture, though in different proportions. The second patient, a 9-month-old male with multiple skeletal abnormalities, showed a 47,XY,+8 and a 47,XXY cell line in both peripheral lymphocytes (61.7% and 38.3%, respectively) and skin fibroblasts (92.8% and 7.2%, respectively). To determine the events underlying the origin of these complex karyotypes we performed Southern blot and polymerase chain reaction (PCR) analysis using polymorphic DNA markers from the X chromosome and from chromosome 8. Both supernumerary chromosomes 8, and, in case 2, the two X chromosomes, appeared to be identical, lacking detectable recombination events. We conclude that, in both cases, the most likely mechanism underlying the origin of the mosaic cell lines was formation of a normal zygote, followed by mitotic errors during early divisions.
 ...
PMID:Double autosomal/gonosomal mosaic aneuploidy: study of nondisjunction in two cases with trisomy of chromosome 8. 775 72

We describe a pedigree presenting X-linked severe mental retardation associated with multiple congenital abnormalities and 46,XY gonadal dysgenesis, leading in one family member to female gender assignment. Female carriers are unaffected. The dysmorphic features are similar to those described in the alpha-thalassemia and mental retardation (ATR-X) syndrome, although there is no clinical evidence of alpha-thalassemia in this family. In addition, the family had other clinical features not previously observed in the ATR-X syndrome, including partial optic-nerve atrophy and partial ocular albinism. Mutations in a putative DNA helicase, termed XH2, have been reported to give rise to the ATR-X syndrome. We screened the XH2 gene for mutations in affected members of the family and identified a 4-bp deletion at an intron/exon boundary that removes an invariant 3' splice-acceptor site. The mutation cosegregates with the syndrome. The genomic deletion causes missplicing of the pre-mRNA, which results in the loss of 8 bp of coding sequence, thereby generating a frameshift and a downstream premature stop codon. Our finding increases the range of clinical features associated with mutations in the XH2 gene.
 ...
PMID:A novel mutation in the putative DNA helicase XH2 is responsible for male-to-female sex reversal associated with an atypical form of the ATR-X syndrome. 865 Dec 95

Most phenotypic females with an XY male karyotype do not have significant extragenital anomalies; however, some patients with additional abnormalities have been described. We report on an individual with XY gonadal dysgenesis, mental retardation, microcephaly, growth retardation, and multiple pterygia. Although not previously reported, the possible relationship between these findings is discussed in the context of evident heterogeneity of XY gonadal dysgenesis.
 ...
PMID:XY gonadal dysgenesis associated with a multiple pterygium syndrome phenotype. 898 68

In 46,XY individuals, testes are determined by the activity of the SRY gene (sex-determining region Y), located on the short arm of the Y chromosome. The other genetic components of the cascade that leads to testis formation are unknown and may be located on the X chromosome or on the autosomes. Evidence for the existence of several loci associated with failure of male sexual development is indicated by reports of 46,XY gonadal dysgenesis associated with structural abnormalities of the X chromosome or of autosomes (chromosomes 9, 10, 11 and 17). In this report, we describe the investigation of a child presenting with multiple congenital abnormalities, mental retardation and partial testicular failure. The patient had a homogeneous de novo 46,XY,inv dup(9)(pter-->p24.1::p21.1-->p23.3::p24.1-->qter) chromosome complement. No deletion was found by either cytogenetic or molecular analysis. The SRY gene and DSS region showed no abnormalities. Southern blotting dosage analysis with 9p probes and fluorescent in situ hybridisation data indicated that the distal breakpoint of the duplicated fragment was located at 9p24.1, proximal to the SNF2 gene. We therefore suggest that a gene involved in normal testicular development and/or maintenance is present at this position on chromosome 9.
 ...
PMID:Failure of testicular development associated with a rearrangement of 9p24.1 proximal to the SNF2 gene. 952 82


1 2 Next >>