Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An X-linked recessive disease with, in almost all patients, a fatal course in early childhood, occurring in a five-generation family is described. The 12 affected boys had early-onset floppiness, ataxia, liability to infections especially of the upper respiratory tract, deafness, and later, a flaccid tetraplegia and areflexia. Eleven boys died before the age of 5 years. One boy is still alive at the age of 12 years, but in addition to the above-mentioned signs, he must be ventilated at night and is nearly blind due to optic atrophy. In the only patient whose central nervous system could be examined at the time of autopsy, an almost complete absence of myelin in the posterior columns of the spinal cord was found. This may be the main pathological substrate for the neurological findings. No biochemical or immunological defects were detected. The family also counted 16 healthy male siblings and 13 definite of 28 possible female carriers. Some carriers developed a hearing impairment in early adulthood. As far as is known now, this disease has not been described before.
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PMID:X-linked ataxia, weakness, deafness, and loss of vision in early childhood with a fatal course. 849 30

We examined a large family in which an X-linked recessive congenital ataxia manifested in 7 males from three generations. The affected boys first exhibited a marked delay of early developmental motor milestones. A neurological syndrome became evident by 5 to 7 years of age and included cerebellar ataxia, dysarthria, and external ophthalmoplegia; there were no symptoms of mental retardation, spastic paraparesis, or sensory loss. Neuroimaging studies revealed hypoplasia of cerebellar hemispheres and vermis. The disease showed no progression beyond early childhood. The unique heredity and clinical features clearly distinguish this new entity from a variety of previously described familial ataxias. Pairwise linkage analysis and haplotype reconstruction allowed us to map the gene responsible for this disorder to a 38-cM interval on chromosome Xp11.21-q24 flanked by the loci DXS991 and DXS1001. Upon multipoint linkage analysis, the disease gene was determined to be located most likely in the proximal part of chromosome Xq, with the maximal lod score of 4.66 at the locus DXS1059 (Xq23). This is the first example of the genetic mapping of a pure congenital cerebellar hypoplasia syndrome.
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PMID:X-linked nonprogressive congenital cerebellar hypoplasia: clinical description and mapping to chromosome Xq. 868 95

X-linked spinal and bulbar muscular atrophy (SBMA) occurs due to an expansion of the trinucleotide repeat (CAG)n in the androgen receptor gene. Anticipation is relatively rare in SBMA in contrast to spinocerebellar ataxia type 1 (SCAl), and dentatorubral and pallidoluysian atrophy (DRPLA) which show obvious paternal anticipation. The differences in the CAG repeat number were compared among sperm, leukocytes and skeletal muscles of SBMA patients. In SBMA, the sperm of most patients and the skeletal muscle of all patients showed the same repeat number as their leukocytes, whereas the increase in the repeat number from leukocytes to sperm was evident in SCA1 and DRPLA patients. The higher mosaicism level in sperm compared with leukocytes was common in SBMA, SCA1 and DRPLA, and the level of sperm was lower in SBMA than in SCA1 and DRPLA. Thus, spermatogenesis was suggested to be strongly associated with paternal anticipation. The mosaicism level was smaller in SBMA than in other (CAG)n expanded disorders, and smallest in the SBMA carrier females. These findings demonstrate that the CAG repeat in SBMA is relatively stable in mitotic and meiotic, processes, and there is a possibility that the lower mosaicism level of the carrier females compared with the SBMA patients is associated with X-linked recessive inheritance.
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PMID:Mitotic and meiotic stability of the CAG repeat in the X-linked spinal and bulbar muscular atrophy gene. 894 11

There was performed the examination of a family with innate cerebellar hypoplasia. The disease was manifested in 7 males from 3 generations. X-linked recessive type of transmission of mutant gene was established. Clinical syndrome was characterized by delay of motor development during the first year of child's living as well as by ataxia, dysarthria, external ophthalmoplegia and nonprogressive course too. The signs of pronounced hypoplasia of hemispheres and vermis were found by means of computer and magneto-resonance investigation. Molecular genetic study (linkage-analysis) revealed that the gene of the disease was localized in proximal part of long X-chromosome's shoulder, exactly in XpII 21-q24 interval (38 centimorgan genetic distance). That was the first example of successful genetic mapping of the disease from the group of hereditary cerebellar hypoplasias.
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PMID:[A new form of hereditary ataxia: X-linked congenital cerebellar hypoplasia (a clinical and molecular genetic analysis)]. 942 42

By the introduction of technological advancement in methods of structural analysis, electronics, and recombinant DNA techniques, research in physiology has become molecular. Additionally, focus of interest has been moving away from classical physiology to become increasingly centered on mechanisms of disease. A wonderful example for this development, as evident by this review, is the field of ion channel research which would not be nearly as advanced had it not been for human diseases to clarify. It is for this reason that structure-function relationships and ion channel electrophysiology cannot be separated from the genetic and clinical description of ion channelopathies. Unique among reviews of this topic is that all known human hereditary diseases of voltage-gated ion channels are described covering various fields of medicine such as neurology (nocturnal frontal lobe epilepsy, benign neonatal convulsions, episodic ataxia, hemiplegic migraine, deafness, stationary night blindness), nephrology (X-linked recessive nephrolithiasis, Bartter), myology (hypokalemic and hyperkalemic periodic paralysis, myotonia congenita, paramyotonia, malignant hyperthermia), cardiology (LQT syndrome), and interesting parallels in mechanisms of disease emphasized. Likewise, all types of voltage-gated ion channels for cations (sodium, calcium, and potassium channels) and anions (chloride channels) are described together with all knowledge about pharmacology, structure, expression, isoforms, and encoding genes.
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PMID:Voltage-gated ion channels and hereditary disease. 1050 36

The present authors studied a 55-year-old-patient homozygous for the SCA6 gene who experienced frequent attacks of positional vertigo at 37 years of age with subsequent staggering gait and night blindness. Retinitis pigmentosa (RP), as well as cerebellar ataxia and vertical antidirectional nystagmus, were detected. The subject's parents were first cousins, and two of his three male cousins, whose parents were also first cousins, had RP without ataxia or nystagmus. The numbers of CAG repeats in the expanded alleles of the SCA6 gene found by molecular analysis were 21 and 21. The genetic results were negative for SCA1, SCA2, SCA3, SCA7 and dentatorubral pallidoluysian atrophy. The retinal degeneration in this patient is most likely to be secondary to a genetic disorder of autosomal or X-linked recessive inheritance rather than SCA6. Other reported cases of patients homozygous for the SCA6 gene are also reviewed.
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PMID:A patient homozygous for the SCA6 gene with retinitis pigmentosa. 1208 23

Harlequin (Hq) mice develop ataxia due to an X-linked recessive mutation in the gene encoding apoptosis-inducing factor (Aif). Brain cells in Hq mice contain the modified base 8-hydroxydeoxyguanosine (8-OHdG), suggesting that the defect in Aif causes increased DNA oxidation in these cells. Because oxidative damage is mutagenic, Hq mice might suffer increased mutation in the brain. To examine this possibility, mutation in the brain was assessed using the Tg(betaA-G11PLAP) mouse model, which allows mutant cells to be visualized in tissue sections in situ. Hq mice exhibited more and larger patches of PLAP positive tissue in the brain. PLAP+ cells were observed in all areas of the brain. No increase in the number of PLAP+ cells was seen in three other tissues, suggesting that the effect of Aif deficiency on mutation was specific to brain.
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PMID:Increased mutation in mice genetically predisposed to oxidative damage in the brain. 1549 40

Pelizaeus-Merzbacher disease (PMD) is a rare X-linked recessive disorder with a prototype of a dysmyelinating leukodystrophy that is caused by a mutation in the proteolipid protein 1 (PLP1) gene on the long arm of the X chromosome in band Xq22. This mutation results in abnormal expression or production of PLP. We here present a Korean boy with spastic quadriplegia, horizontal nystagmus, saccadic gaze, intentional tremor, head titubation, ataxia, and developmental delay. The brain magnetic resonance imaging (MRI) showed abnormally high signal intensities in the white matter tract, including a subcortical U fiber on the T2-weighted and fluid attenuated inversion recovery (FLAIR) image. The chromosomal analysis was normal; however, duplication of the PLP1 gene in chromosome Xq22 was detected when the multiplex ligation-dependent probe amplification (MLPA) method was used. We also investigated the pedigree for a genetic study related to PMD. This case suggests that the duplication mutation of the PLP1 gene in patients with PMD results in a mild clinical form of the disorder that mimics the spastic quadriplegia of cerebral palsy.
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PMID:Identification of proteolipid protein 1 gene duplication by multiplex ligation-dependent probe amplification: first report of genetically confirmed family of Pelizaeus-Merzbacher disease in Korea. 1843 21

Joubert syndrome (JS) and related disorders (JSRD) are a group of developmental delay/multiple congenital anomalies syndromes in which the obligatory hallmark is the molar tooth sign (MTS), a complex midbrain-hindbrain malformation visible on brain imaging, first recognized in JS. Estimates of the incidence of JSRD range between 1/80,000 and 1/100,000 live births, although these figures may represent an underestimate. The neurological features of JSRD include hypotonia, ataxia, developmental delay, intellectual disability, abnormal eye movements, and neonatal breathing dysregulation. These may be associated with multiorgan involvement, mainly retinal dystrophy, nephronophthisis, hepatic fibrosis and polydactyly, with both inter- and intra-familial variability. JSRD are classified in six phenotypic subgroups: Pure JS; JS with ocular defect; JS with renal defect; JS with oculorenal defects; JS with hepatic defect; JS with orofaciodigital defects. With the exception of rare X-linked recessive cases, JSRD follow autosomal recessive inheritance and are genetically heterogeneous. Ten causative genes have been identified to date, all encoding for proteins of the primary cilium or the centrosome, making JSRD part of an expanding group of diseases called "ciliopathies". Mutational analysis of causative genes is available in few laboratories worldwide on a diagnostic or research basis. Differential diagnosis must consider in particular the other ciliopathies (such as nephronophthisis and Senior-Loken syndrome), distinct cerebellar and brainstem congenital defects and disorders with cerebro-oculo-renal manifestations. Recurrence risk is 25% in most families, although X-linked inheritance should also be considered. The identification of the molecular defect in couples at risk allows early prenatal genetic testing, whereas fetal brain neuroimaging may remain uninformative until the end of the second trimester of pregnancy. Detection of the MTS should be followed by a diagnostic protocol to assess multiorgan involvement. Optimal management requires a multidisciplinary approach, with particular attention to respiratory and feeding problems in neonates and infants. Cognitive and behavioral assessments are also recommended to provide young patients with adequate neuropsychological support and rehabilitation. After the first months of life, global prognosis varies considerably among JSRD subgroups, depending on the extent and severity of organ involvement.
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PMID:Joubert Syndrome and related disorders. 2061 30

Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive disorder affecting myelination of the central nervous system, and is caused by mutations of the proteolipid protein 1 (PLP1) gene. Clinical manifestations of PMD are variable and major features include progressive nystagmus, spasticity, tremor, ataxia, and psychomotor delay. We describe a classical PMD patient who had been misdiagnosed as cerebral palsy. He had nystagmus and psychomotor delay since infancy and tremor with ataxia developing gradually. Brain MRI revealed demyelination over white matter of the cerebral hemispheres and posterior limbs of the internal capsules. Positive family history led to subsequent mutation analysis, which identified a novel mutation (c.88G>C) in PLP1 in the proband, as well as his affected brother and maternal uncle, and asymptomatic maternal grandmother, mother and two sisters. Therefore, PMD should be considered in a cerebral palsy-like patient with or without positive family history. Mutation analysis is crucial for early diagnosis and further genetic counseling.
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PMID:Pelizaeus-Merzbacher disease, easily misdiagnosed as cerebral palsy: a report of a three-generation family. 2359 42


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