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Results for “X-Linked Intellectual Disability”

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At least 37 records · Page 2Linked to original sources
PubMed1978

Inherited congenital normofunctional testicular hyperplasia and mental deficiency. A corroborative study.

Three 46,XY unrelated individuals out of 84 postpubertal male inpatients with severe mental deficiency in a psychiatric hospital were found to have megalorchidia and macrogenitosomia. One of the cases had a similarly affected brother. Endocrine studies were performed in two of the cases with similar results. Normal plasma levels of pituitary gonadotropins were found. A normal testicular function was demonstrated by the finding of normal: (a) baseline plasma testosterone levels and a significant rise following human chorionic gonadotropin administration, (b) sperm analysis, and (c) morphology and cell architecture of the testes. These results were compatible with normofunctional testicular hyperplasia confirming previous observations and allowing the definite individualization of a syndrome with mental deficiency probably due to an X-linked recessive mutation.

Adult↗
PubMed2025

KLHL13 functional defects cause neurodevelopmental disorder in humans that can be rescued via inhibition of AURKB in cellular and animal models.

PURPOSE: Neurodevelopmental disorders (NDDs) are characterized by limitations in brain development. This study aims to determine the genetic causes of NDD in humans. METHODS: Exome sequencing was used to detect genetic variants of KLHL13, which encodes Kelch like protein 13 (KLHL13), in four families segregating in an X-linked pattern. In silico protein modeling and overexpression in heterologous cells were used to determine the variant's impact. klhl13 loss of function was modeled in zebrafish, followed by rescue studies using human KLHL13 messenger RNA (mRNA) and an Aurora Kinase B (AURKB) inhibitor. RESULTS: We found one frameshift and three missense hemizygous variants of KLHL13 in individuals exhibiting NDD characteristics, such as intellectual disability (ID) and macrocephaly. Three-dimensional protein modeling simulation predicted the alteration of the KLHL13 protein folding for missense variants. Overexpression of NDD-associated variants in HEK293T cells revealed a significant impact on KLHL13-mediated cell-cycle regulation during mitosis, leading to genomic instability. Knocking down klhl13 in zebrafish resulted in developmental deficits, which were rescued by coinjection of human KLHL13WT messenger RNA but not by transcript encoding NDD variants. Treatment with AURKB selective inhibitor AZD1152-HQPA rescued genomic stability in heterologous cells and neurobehavioral deficits in zebrafish. CONCLUSION: Our results implicate KLHL13-mediated AURKB regulation as a significant contributor to NDD in humans. Inhibiting AURKB activity could serve as a potential therapeutic approach to improve brain development and cognitive function.

Humans↗
PubMed1978

X-Y translocation in a retarded phenotypic male. Clinical, cytogenetic, biochemical, and serogenetic studies.

Cytogenetic studies on a mentally retarded boy revealed an X-Y translocation, karyotype 46,X,t(X;Y)(p22;q11). Only 5 other such cases have been reported and these were all females. The unequivocal male phenotype suggested non-random inactivation of the normal maternally derived X chromosome, and that the non-inactivated X-Y translocation chromosome included the locus for male determination. Confirmation of this was provided by unassociated X and Y chromatin in interphase cells, as well as by reverse banding after BrdU incorporation and autoradiography of metaphase chromosomes. There was anomalous Xg blood group inheritance in the proband, indicating possible localisation of the Xg locus to the terminal portion of the X short arm. Linkage of Xg and a form of X-linked mental retardation is suggested. Close linkage of the Xg locus with the loci for alpha-galactosidase, phosphoglycerate kinase, G-6-PD, and MPS II was excluded.

Blood Group Antigens↗
PubMed1977

X-linked mental deficiency megalotestes syndrome.

Members of two kindreds had mental deficiency and megalotestes. The familial occurrence suggests an X-linked recessive trait or autosomal-dominant trait with male sex limitation. The increased testicular size was apparently due to excess fluid content.

Abnormalities, Multiple↗
PubMed1979

X-linked hypogonadism, gynecomastia, mental retardation, short stature, and obesity--a new syndrome.

Five male members in four generations of the same family had hypogonadism, gynecomastia, mental retardation, obesity, and short stature. The X-linked mode of inheritance, the distinctive facies, the normal size of the hands and feet, and the true gynecomastia are the main characteristics. Endocrine evaluation and histologic studies of the testes suggest partial hypogonadotropic hypogonadism. This disorder represents a new syndrome distinct from others previously described.

Adult↗
PubMed1979

A presumptive new variant of Norrie's disease.

The present report describes a Brazilian Negro sibship with six males affected by a presumptive new variant of Norrie's disease, an X-linked congenital oculo-acoustical-cerebral degeneration. In addition to the typical stigmata of the disease, all the patients were microcephalic and two of them had cryptorchidism. Possible non-genetic aetiology was investigated with negative results. Xg blood group studies were informative and the lod scores are given, together with those for two previously reported families with Norrie's disease.

Adolescent↗
PubMed1977

An etiological survey of the severely retarded Hertfordshire children who were born between January 1, 1965 and December 31, 1967.

An etiological survey is presented of all suveryl retarded children living in Hertfordshire, at home and in residential care, born between January 1, 1965, and December 31, 1967. One hundred and forty-six children (87 boys and 59 girls) were ascertained, out of a total population of 46,960, with a prevalence of 1 in 320 or 3.1 per 1,000. Approximately 1/3 (47) had the Down syndrome, 1 per 1,000 population. It was possible to establish a diagnosis in a further 45 cases, which included 1 additional case of autosomal chromosome abnormality and 7 each of autosomal dominant, recessive and X-linked conditions; 17 were associated with presumed multifactorial etiological factors; in 6 the condition was thought to have been caused by an environmental agent. It was not possible to establish a cause in the remaining 54 cases. Recurrence risks of severe mental retardation in cases where it is possible to establish a definite diagnosis are discussed and the potential value, for genetic counseling purposes, of a categorizing such patients into broad symptomatological groups, is suggested.

Dermatoglyphics↗
PubMed1978

The X-linked syndrome of macroorchidism and mental retardation: further observations.

We report six males with the syndrome of macroorchidism and mental retardation. The trait is inherited as though X-linked, or possibly autosomal dominant male-limited. We also found no evidence of gonadal dysfunction. Associated abnormalities were abnormal EEG (3/4), seizures (2/6), and one instance each of cervical vertebral fusion, cataract, esophoria, and abnormal cutaneous pigmentation. One woman with a 50% a priori risk of bearing the mutant gene had mental retardation and seizures. Results of Xg blood-group typing were uninformative for the purpose of linkage analysis.

Abnormalities, Multiple↗
PubMed1977

The FG syndrome: further characterization, report of a third family, and of a sporadic case.

We report 5 new cases of the FG syndrome, 1 sporadic, 3 brothers from a European family, and another affected male born in the first FG syndrome family reported by Opitz and Kaveggia in 1974. The pedigree data confirm the hypothesis of X-linked inheritance of this multiple congenital anomaly/mental retardation (MCA/MR) syndrome. Its manifestations include shortness of stature with a disproportionately large head, mental retardation, hypotonia with or without congenital joint contractures, seizures and a strikingly characteristic personality of facial appearance, imperforate anus and/or orthe gastrointestinal defects, congenital heart defects, and many minor manifestations. Chronic pulmonary disease in some affected males may be a complication of hypotonia.

Abnormalities, Multiple↗
PubMed1979

Heritable fragile sites on human chromosomes. III. Detection of fra(X)(q27) in males with X-linked mental retardation and in their female relatives.

The fragile site at Xq27 which is associated with X-linked retardation with macroorchidism has been studied in 21 retarded males. These males were from 12 families, and studies of nine of the familes were possible. Detection of carrier females is difficult, especially with increasing age. The fragile site was demonstrated in only five of 13 obligate carrier females. It is concluded that using present methods, cytogenetic detection of carriers is fairly reliable in females aged less than 20--25 years but unreliable in older females.

Adolescent↗
PubMedDate not supplied

Reliability of Békésy threshold tracing in identification of carriers of genes for an X-linked disease with deafness.

Seven identified carriers and 20 potential carriers of Norris's disease have been examined by pure tone octave audiometry and Békésy audiometry. The investigation supports earlier results of Békésy threshold tracings performed in heterozygote carriers of genes for recessive hearing impairment. The sensitivity of the method is poor. The specificity of the Békésy threshold tracing is high, meaning that an absent dip cannot exclude the possibility of a subject being a carrier, whereas a present dip can be regarded as an indication of carrier. When comparing conventional octave audiometry and Békésy threshold tracing, the latter method is found to be more subtle in finding carriers of genes for recessive deafness. Therefore, Békésy threshold tracing may be of help in the genetic counselling of potential carriers of genes for recessive deafness.

Adolescent↗
PubMed1979

A study of possible heterogeneity in Duchenne muscular dystrophy.

One possible explanation for the apparently high birth incidence of Duchenne muscular dystrophy (DMD), a lethal X-linked disorder, is genetic heterogeneity. As a first step in possibly demonstrating genetic heterogeneity, affected boys were sub-divided into those with and without severe mental handicap. In those with severe mental handicap, ages at onset and of becoming confined to a wheelchair were later, the fall in SCK level with age was less marked, and the urinary excretion of certain aminoacids was greater than in affected boys with normal intelligence. Though the number of subjects investigated was relatively small (15 in each group) and further studies are therefore needed, the results suggest that DMD may not be a single disease entity.

Adolescent↗
PubMed1979

X-linked mental retardation with macro-orchidism and marker X chromosomes.

A family with X-linked mental retardation and a marker X chromosome was ascertained by the presence of macro-orchidism in the three institutionalized probands. Verbal evaluation revealed a generalized language disability with commonly occurring articulation errors. The heterozygous females in this family exhibited some reduction in mental ability; the marker X chromosome was demonstrated in both sexes.

Female↗
PubMed1977

X-linked dysosteosclerosis. Four familial cases.

Four Spanish children with clinical and radiological features corresponding to dysosteosclerosis are presented. All the children were male and belonged to the same family. The first known carrier is the maternal grandmother, who had three daughters by three different fathers who in turn had one or more sons with the disease. The four carriers were normal. Consanguinity did not occur in any case and the disorder was transmitted as a sex-linked recessive condition.

Adolescent↗
PubMed1977

X-linked recessively inherited non-specific mental retardation. Report of a large family.

A large kindred is described in which 22 males and 3 females show non-specific mental retardation with impaired speech. An X-linked recessive is the most likely mode of inheritance of this condition. Similar families have been described in the literature, characteristic physical abnormalities are absent and performance I.Q. tends to be higher than verbal I.Q. This possible heterogenous condition may be a major individual cause of mental deficiency in males, and may account for the excess of male retardates in the population.

Adolescent↗