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Biomedical subjects

E M Valente

Publications and source records attributed to E M Valente.

35 records · Page 2Linked to original sources
PubMed2001

DYT13, a novel primary torsion dystonia locus, maps to chromosome 1p36.13--36.32 in an Italian family with cranial-cervical or upper limb onset.

Primary torsion dystonia (PTD) is a clinically and genetically heterogeneous group of movement disorders, usually inherited in an autosomal dominant fashion with reduced penetrance. The DYT1 gene on chromosome 9q34 is responsible for most cases of early limb-onset PTD. Two other PTD loci have been mapped to date. The DYT6 locus on chromosome 8 is associated with a mixed phenotype, whereas the DYT7 locus on chromosome 18p is associated with adult onset focal cervical dystonia Several families have been described in which linkage to the known PTD loci have been excluded. We identified a large Italian PTD family with 11 definitely affected members. Phenotype was characterized by prominent cranial-cervical and upper limb involvement and mild severity. A genome-wide search was performed in the family. Linkage analysis and haplotype construction allowed us to identify a novel PTD locus (DYT13) within a 22 cM interval on the short arm of chromosome 1, with a maximum lod score of 3.44 between the disease and marker D1S2667.

Adolescent↗
PubMed2000

A Yorkshire family with adult-onset cranio-cervical primary torsion dystonia.

Although a family history is described in approximately 20% of patients, large families with adult-onset craniocervical primary (idiopathic) torsion dystonia (PTD) are rare. We report a new British family with cranio-cervical dystonia. Seventeen members of the family were examined. Five cases were diagnosed as definite PTD and one as probable PTD. Mean age at onset was 29 years (range, 19-40 yrs). The phenotype was characterized by adult-onset cranio-cervical dystonia in all affected cases. A few cases had additional voice tremor and/or postural arm tremor. The GAG deletion in the DYT1 gene was excluded in the index case. Linkage analysis was performed between the disease and several marker loci spanning DYT6 and DYT7 regions, and haplotypes were reconstructed in all subjects. Although linkage analysis was not completely informative, reconstructed haplotypes excluded linkage between the disease and either DYT6 or DYT7. This report confirms that familial cranio-cervical dystonia is genetically heterogeneous, and further studies of other PTD families with similar clinical features are needed to identify other new genes.

Adult↗
PubMed2000

A second paroxysmal kinesigenic choreoathetosis locus (EKD2) mapping on 16q13-q22.1 indicates a family of genes which give rise to paroxysmal disorders on human chromosome 16.

Paroxysmal kinesigenic choreoathetosis (PKC) is a rare paroxysmal movement disorder characterized by recurrent and brief attacks of choreiform or dystonic movements triggered or exacerbated by sudden voluntary movements. Some patients with PKC also have a history of infantile afebrile convulsions. PKC can be sporadic, or familial with autosomal dominant inheritance. PKC has been mapped to the pericentromeric region of human chromosome 16 in several Japanese families and in an African-American family, to regions which overlap by 9.8 cM (centiMorgan). Both regions overlap by 3.4 cM with a region containing a gene responsible for 'infantile convulsions and paroxysmal choreoathetosis' (ICCA). We have identified a second PKC locus (EKD2) on the long arm of chromosome 16 in a large Indian family with PKC. A maximum two-point LOD score of 3.66 (recombination fraction = 0.00, penetrance = 0.80) was obtained between PKC and D16S419. Haplotype and recombinant analysis localized EKD2 to a 15.8 cM region between D16S685 and D16S503. This region does not overlap with that identified in Japanese families, or with the ICCA locus. These results exclude one locus on chromosome 16 which causes both the ICCA and PKC syndromes; this suggests that there may be a cluster of genes on human chromosome 16 which lead to paroxysmal disorders.

Adolescent↗
PubMed2000

A new family with paroxysmal exercise induced dystonia and migraine: a clinical and genetic study.

OBJECTIVE: To characterise the phenotype of a family with paroxysmal exercise induced dystonia (PED) and migraine and establish whether it is linked to the paroxysmal non-kinesigenic dyskinesia (PNKD) locus on chromosome 2q33-35, the familial hemiplegic migraine (FHM) locus on chromosome 19p, or the familial infantile convulsions and paroxysmal choreoathetosis (ICCA syndrome) locus on chromosome 16. METHODS: A family, comprising 30 members, was investigated. Fourteen family members in two generations including three spouses were examined. Haplotypes were reconstructed for all the available family members by typing several microsatellite markers spanning the PNKD, FHM, and ICCA loci. Additionally, the four exons containing the known FHM mutations were sequenced. RESULTS: Of 14 members examined four were definitely affected and one member was affected by history. The transmission pattern in this family was autosomal dominant with reduced penetrance. Mean age of onset in affected members was 12 (range 9-15 years). Male to female ratio was 3:1. Attacks of PED in affected members were predominantly dystonic and lasted between 15 and 30 minutes. They were consistently precipitated by walking but could also occur after other exercise. Generalisation did not occur. Three of the affected members in the family also had migraine without aura. Linkage of the disease to the PNKD, FHM, or ICCA loci was excluded as no common haplotype was shared by all the affected members for each locus. In addition, direct DNA sequential analysis of the FHM gene (CACNL1A4) ruled out all known FHM point mutations. CONCLUSIONS: This family presented with the classic phenotype of PED and is not linked to the PNKD, FHM, or ICCA loci. A new gene, possibly coding for an ion channel, is likely to be the underlying cause of the disease.

Adolescent↗
PubMed1999

Italian family with cranial cervical dystonia: clinical and genetic study.

A white Italian family affected by primary torsion dystonia (PTD) is described. The family phenotype most commonly presented with adult onset, cranial cervical involvement, and focal or segmental distribution without progression to generalization. Thirty-nine family members and nine spouses were studied. Five subjects received a diagnosis of definite PTD, three of probable PTD. Age at onset was in adulthood for all. In four definitely affected subjects, dystonia started in the cranial or cervical districts; in one it presented as writer's cramp. Familial writer's cramp also occurred in the family of the unrelated parent of the latter patient. The mean age at time of examination was 61.8 years in the individuals with a definite diagnosis; 60 in those with a probable diagnosis. At the time of examination, in most of the affected subjects, dystonia was focal; in three cases (two definitely and one probably affected), it was segmental. DNA linkage analysis, although limited by the size of the family, suggested exclusion of linkage between the disease and known PTD loci (DYT6 and DYT7). The GAG deletion in the DYT1 gene was excluded in the proband and in the family member affected by writer's cramp.

Adult↗
PubMed1999

Detailed haplotype analysis in Ashkenazi Jewish and non-Jewish British dystonic patients carrying the GAG deletion in the DYT1 gene: evidence for a limited number of founder mutations.

The DYT1 gene on human chromosome 9q34 appears to be responsible for most cases of early onset primary torsion dystonia (PTD) both in Ashkenazi Jewish (AJ) and in non-Jewish patients. Previous haplotype analysis in a 2 cM region surrounding the DYT1 gene showed that a single founder mutation (DYT1AJ) was responsible for most cases of early onset PTD in the North American AJ population and refined the most likely location of the gene to a 150 kb interval between the marker loci D9S2161 and D9S63. Recently, the majority of cases of early onset PTD in both AJ and non-Jewish patients were found to carry a unique 3-bp (GAG) deletion in the coding region of the DYT1 gene. This deletion appears to have arisen more than once, suggesting independent mutational events. In this study, we analysed the haplotypes surrounding DYT1 in 9 AJ and 15 non-Jewish British patients carrying the GAG deletion in the DYT1 gene. We found that all AJ British patients carried the same haplotype as the North American Jews, sustaining the theory that the current British AJ community descends from the same small group of individuals as the North American Jewry. Furthermore, in the non-Jewish British patients, only a limited number of distinct founder mutations was observed. This supports the hypothesis that the GAG deletion in the DYT1 gene is not a very frequent mutation, and that it has arisen only a limited number of times throughout the centuries.

Alleles↗
PubMed1999

Primary torsion dystonia: the search for genes is not over.

A GAG deletion in the DYT1 gene accounts for most early, limb onset primary torsion dystonia (PTD). The genetic bases for the more common adult onset and focal PTD are less well delineated. Genetic loci for an "intermediate dystonia" phenotype and for torticollis, named DYT6 and DYT7 respectively, have recently been mapped in single families. To evaluate the contribution of these genetic loci to other families with familial "non-DYT1" dystonia five large families with dystonia were studied using genetic markers spanning the DYT6 and DYT7 regions. There was no evidence of linkage to either locus in any family. These findings illustrate the genetic heterogeneity of the dystonias and indicate the existence of one or more as yet unmapped genes for dystonia. Large collaborative efforts will be required to identify these, and additional genes, causing PTD.

Adolescent↗
PubMed1998

Dopa-responsive dystonia: a clinical and molecular genetic study.

We have studied the GTP-cyclohydrolase 1 (GCH-1) gene in 30 patients with the diagnosis of clinically definite (n = 20) or possible (n = 10) dopa-responsive dystonia (DRD) as well as in a child with atypical phenylketonuria due to complete GCH-1 deficiency. A large number of new heterozygote mutations (seven point mutations, two splice site mutations, and one deletion) as well as a new homozygote mutation in the child with atypical phenylketonuria were detected. In addition, two previously described mutations were found in two other cases. We further extended our investigation of GCH-1 to the 5' and 3' regulatory regions and report the first detection of point mutations in the 5' untranslated region. Demethylation of CpG islands does not appear to be an important causative factor for the GCH-1 mutations in DRD. In addition, we have extended the clinical phenotype of genetically proven DRD to focal dystonia, dystonia with relapsing and remitting course, and DRD with onset in the first week of life. None of our DRD patients without a mutation in GCH-1 had the 3-bp deletion recently detected in DYT1, the causative gene for idiopathic torsion dystonia with linkage to 9q34.

5' Untranslated Regions↗
PubMed1998

The role of DYT1 in primary torsion dystonia in Europe.

Primary torsion dystonia (PTD) is a clinically and genetically heterogeneous movement disorder. DYT1 on chromosome 9q34 was the first PTD gene to be mapped. A 3-bp (GAG) deletion in this gene was reported to account for almost all early limb-onset generalized PTD. No relationship has been found with DYT1 in patients with prominent craniocervical involvement. To elucidate the DYT1-associated phenotype, we analysed the DYT1 mutation in 150 PTD patients, either sporadic or index cases from small PTD families. Twenty-two patients were positive for the GAG deletion in the DYT1 gene. Fifteen of them presented with the typical DYT1 phenotype (early, limb-onset generalized dystonia without spread to craniocervical muscles), four had limb-onset dystonia with spread to craniocervical muscles, two patients had arm-onset segmental dystonia and one had focal right-arm dystonia. One-hundred and twenty-eight patients were negative for the DYT1 mutation. Forty-six of them had segmental dystonia and 59 had focal dystonia. The other 23 patients presented with generalized dystonia, either with craniocervical involvement (13 patients) or without spread to the craniocervical region (typical DYT1 phenotype-10 patients). These data confirm the importance of the GAG deletion in European cases of PTD, and indicate phenotypic and genotypic heterogeneity.

Adolescent↗
PubMed1997

Neurophysiological classification and sensitivity in 500 carpal tunnel syndrome hands.

OBJECTIVES: To evaluate the following points about carpal tunnel syndrome (CTS): 1) characterization of a wide population; 2) sensitivity of electrodiagnostic tests, and particularly the contribution of disto-proximal ratio test; 3) validity of a neurophysiological classification developed by us. MATERIAL AND METHODS: Prospective study in 500 hands with CTS symptoms. Neurophysiological "standard" tests were always performed: sensory nerve conduction velocity (SNCV) first- and third digit-wrist and distal motor latency (DML). In "standard negative" hands disto-proximal ratio technique (R) was performed. Neurophysiological classification: Extreme CTS (absence of median motor, sensory responses), Severe (absence of sensory response, abnormal DML), Moderate (abnormal SNCV, abnormal DML), Mild (abnormal SNCV, normal DML), Minimal (abnormal R or other segmental/comparative test, normal standard tests). RESULTS: Sensibility of standard tests: 77%. R increased the diagnostic yield by 20%. CTS classification appeared reliable with significant differences between groups. CONCLUSION: R is a useful test, the classification may be useful in clinical/therapeutical decisions.

Adult↗
PubMed1996

A useful electrophysiologic parameter for diagnosis of carpal tunnel syndrome.

In 43 patients (50 hands) with clinical manifestations of mild-moderate carpal tunnel syndrome (CTS) and 36 healthy volunteers (40 hands), orthodromic sensory nerve conduction velocity (SNCV) was measured with surface electrodes in the median nerve between the third digit and palm and between the palm and wrist. These figures were used to calculate the ratio of distal to proximal conduction (distoproximal ratio). All 90 hands were also subjected to other nerve conduction studies used for diagnosis of CTS. All control hands presented distoproximal ratios < 1.0 reflecting higher conduction rates in the proximal segment. In contrast, 49 of 50 CTS hands (98%) presented reversed ratios (> 1.0) indicating compromised proximal conduction. The sensitivity of this test was significantly greater than that of other methods evaluated, including comparative studies and segmental study of the palm-wrist portion of the median nerve. Segmental study of median SNCV with calculation of the distoproximal ratio is a sensitive technique for diagnosis of CTS in patients with normal findings in standard nerve conduction studies.

Adult↗
PubMed1996

Low-rate nerve stimulation during regional ischemia in the diagnosis of muscle glycogenosis.

Five patients with muscle glycogenoses (Gly), 30 normal subjects (NS), and 52 disease controls received 3 Hz repetitive stimulation of the ulnar nerve for 4 min (P-LRNS) during regional ischemia and during normal circulation. During regional ischemia, the compound muscle action potential (CMAP) of NS showed 8.5% (SE: 1.0) facilitation after 1 min of P-LRNS and 4.8 +/- 1.5% facilitation after 4 min. Gly showed 8.1 +/- 1.0% facilitation after 1 min of P-LRNS but -58.6 +/- 6.9% depression after 4 min of P-LRNS. During normal circulation, in 18 NS and 4 Gly tested, the facilitation detected after 1 min of P-LRNS was unchanged until the end of stimulation. Compared with the mean +/- 2 SD of NS, individual values of CMAP depression were abnormal in all Gly patients already by the 3rd min of ischemic P-LRNS. Of disease controls, myasthenia gravis patients only showed a CMAP depression during ischemic P-LRNS which was distinguishable from that detected in Gly, being mainly induced by neuromuscular transmission block.

Action Potentials↗
PubMed1996

Surgical prognosis in carpal tunnel syndrome: usefulness of a preoperative neurophysiological assessment.

In this study 37 CTS hands underwent pre- and post-operative (15 days 2 and 6 months) evaluation of median nerve distal motor latency (DML) and sensory nerve conduction velocities (SNCV: I digit and III digit-wrist). Pre-operatively, CTS hands were classified as mild (decreased SNCV, normal DML), moderate (decreased SNCV, increased DML) or severe (absent sensory nerve action potentials, increased DML). Post-operatively, all hands presented clinical and neurophysiological improvement. The three groups of patient showed different clinical and neurophysiological responses to nerve decompression: we observed a rapid restitutio ad integrum in mild group, an improvement with normalisation in about 50% of the hands in moderate group, and a high percentage of restore of the sensory responses with no normalisation in severe group. A marked improvement of sensory symptoms was observed in all cases, but some degree of motor and/or sensory deficit was still present six months after surgery in more advanced cases. Preoperative electrophysiological assessment of median nerve function in CTS hands have an important role in predicting the outcome of surgical decompression.

Adult↗