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M Topcu

Publications and source records attributed to M Topcu.

16 recordsLinked to original sources
PubMed2005

Two novel CLN6 mutations in variant late-infantile neuronal ceroid lipofuscinosis patients of Turkish origin.

Neuronal ceroid lipofuscinoses (NCLs) are the most common neurodegenerative childhood-onset disorders characterized by autosomal recessive inheritance, epileptic seizures, progressive psychomotor deterioration, visual failure, and premature death. At least seven subtypes of childhood-onset NCLs have been identified of which the late-infantile-onset forms (LINCLs) are genetically the most heterogeneous with four underlying genes identified. A variant form of LINCL (vLINCL) present in Turkish patients has been considered a distinct clinical and genetic entity (CLN7). However, we recently showed that mutations in the CLN8 gene account for a subset of Turkish vLINCL. Toward identifying the CLN7 gene we here screened the known NCL loci for homozygosity in nine Turkish vLINCL families. These loci were excluded in seven families that are likely to represent the 'true' Turkish vLINCL. In two families, we identified two novel homozygous mutations in the CLN6 gene: an intronic base substitution (c.542+5G>T) affecting the splicing of the transcript and a nonsense mutation (c.663C>G) creating a stop codon at tyrosine 221. These data indicate that CLN6 mutations, in addition to those of CLN8, should be considered a diagnostic alternative in Turkish vLINCL patients. The genetic background of the 'true' Turkish vLINCL, CLN7, remains to be defined.

Age of Onset↗
PubMed2005

Giant axonal neuropathy: clinical and genetic study in six cases.

BACKGROUND: Giant axonal neuropathy (GAN) is a severe recessive disorder characterised by variable combination of progressive sensory motor neuropathy, central nervous system (CNS) involvement, and "frizzly" hair. The disease is caused by GAN gene mutations on chromosome 16q24.1. AIMS: To search for GAN gene mutations in Turkish patients with GAN and characterise the phenotype associated with them. METHODS: Linkage and mutation analyses were performed in six affected patients from three consanguineous families. These patients were also investigated by cranial magnetic resonance imaging (MRI) and electroencephalography (EEG). Electromyography (EMG) was performed in heterozygous carriers from family 1 and family 3. RESULTS: Linkage to 16q24.1 was confirmed by haplotype analysis. GAN mutations were identified in all families. Family 1 had the R293X mutation, previously reported in another Turkish family. Families 2 and 3, originating from close geographical areas, shared a novel mutation, 1502+1G>T, at the donor splice site of exon 9. All patients displayed a common phenotype, including peripheral neuropathy, cerebellar ataxia, and frizzly hair. Cranial MRI showed diffuse white matter abnormalities in two patients from family 1 and the patient from family 3, and minimal white matter involvement in the patient from family 2. EMG of a heterozygous R293X mutation carrier showed signs of mild axonal neuropathy, whereas a 1502+1G>T mutation carrier had normal EMG. EEG abnormalities were found in three patients. CONCLUSION: These findings highlight the association of CNS involvement, in particular white matter abnormalities, with peripheral neuropathy in GAN. The phenotypical consequences of both mutations (when homozygous) were similar.

Adolescent↗
PubMed2004

Bilateral generalized polymicrogyria (BGP): a distinct syndrome of cortical malformation.

BACKGROUND: Syndromes of bilateral symmetric polymicrogyria include an autosomal recessive form of bilateral frontoparietal polymicrogyria (BFPP), in which the malformation is most severe rostrally. The authors describe a new syndrome they have termed "bilateral generalized polymicrogyria" (BGP), in which the malformation occurs in a generalized distribution but is often most severe in the perisylvian regions. METHODS: Patients with bilateral polymicrogyria were identified from multiple medical centers worldwide. The diagnosis of BGP was based on findings from conventional spin echo MRI and, in one case, postmortem neuropathologic findings. Genetic analysis was performed for those patients from consanguineous pedigrees and those with multiple affected siblings to rule out linkage to the BFPP locus on chromosome 16q. RESULTS: Twelve patients were identified with BGP. Clinical features included cognitive and motor delay as well as seizures. Some specific features characteristic of other known bilateral polymicrogyria syndromes, such as pseudobulbar palsy and dysconjugate gaze, were not commonly seen in these patients. Radiologically, polymicrogyria appeared widespread but was often most severe in the perisylvian regions. Pathologic examination in one case revealed a diffusely thin and excessively folded cerebral cortex lacking normal six-layered architecture. Seven patients subjected to genetic analysis did not demonstrate linkage to the BFPP locus. CONCLUSIONS: BGP is a distinct syndrome of cortical malformation. Several features allow BGP to be distinguished from other disorders on the growing list of bilateral symmetric polymicrogyria syndromes.

Abnormalities, Multiple↗
PubMed2002

D-glyceric aciduria in a six-month-old boy presenting with West syndrome and autistic behaviour.

D-Glyceric aciduria is a disease with a very heterogeneous group of symptoms, with D-glyceric acid excretion as the chief common characteristic. Findings described in previous patients include progressive neurological impairment, hypotonia, seizures, failure to thrive and metabolic acidosis. However, there are also asymptomatic patients with mild neurological impairment. A six-month-old boy was admitted to our clinic with the complaints of dullness to his environment, seizures and autistic behaviour. EEG revealed multifocal generalized epileptic activity in a hypsarrhythmia pattern. Organic acid analysis (GC-MS) in urine revealed increased glyceric acid excretion. Analysis of the optical form of glyceric acid by a polarimetric method supported the diagnosis of D-glyceric aciduria. MRI showed white matter lesions with cerebral atrophy, particularly in the frontotemporal regions, and reversible abnormalities in the mesencephalon, thalami and globus pallidium resolving after fructose restriction in the diet. To our knowledge, this is the first case report of a patient with D-glyceric aciduria who presented with West syndrome and autistic behaviour in whom serial MRI findings are also defined.

Autistic Disorder↗
PubMed2001

Effects of Johnstone pressure splints combined with neurodevelopmental therapy on spasticity and cutaneous sensory inputs in spastic cerebral palsy.

The purpose of this study was to investigate the effectiveness of Johnstone pressure splints (JPSs) on spasticity and cutaneous sensory inputs in children with spastic cerebral palsy (CP). Thirty-four children with spastic diplegic CP participated in this study. Children whose motor development levels were similar were divided into a treatment and a control group. Each group consisted of 17 participants (six females and 11 males). Mean age of the treatment group was 48.82 months (SEM 4.42), and the control group, 47.52 months (SEM 5.27). The treatment group underwent Bobath's neurodevelopmental therapy (NDT) combined with JPSs. The control group underwent NDT alone five days a week for three months. Before and after treatments, lower-extremity passive range of motion (ROM) by goniometric measurements, spasticity by Modified Ashworth Scale (MAS), and somatosensory evoked potentials (SEPs) were measured. Passive ROM showed significant improvements in both groups (p<0.01). In the treatment group, all MAS scores increased. In the control group, the difference was significant except for values of internal rotator muscles. Improvements in passive ROM in the treatment group were significantly higher than the control group except in hip abduction and external rotation (p<0.05). MAS scores of the treatment group were significantly higher than the control group (p<0.05). SEP values increased in both groups but values of the treatment group were significantly higher than the control group (p<0.05).

Cerebral Palsy↗
PubMed2001

Molybdenum cofactor deficiency: report of three cases presenting as hypoxic-ischemic encephalopathy.

We report three infants with the diagnosis of molybdenum cofactor deficiency. The key findings leading to diagnosis were neonatal seizures unresponsive to treatment, craniofacial dysmorphic features, hyperexcitability, low blood uric acid levels, and neuroimaging findings. The parents were consanguineous in two of these patients. The diagnosis was established by the presence of low blood uric acid levels, positive urine sulfite reaction, quantitative aminoacid analysis, and high-voltage electrophoresis of the urine sample showing a typical increase of S-sulfo-L-cysteine. Skin fibroblast cultures confirmed the diagnosis. Magnetic resonance imaging findings were suggestive of encephalomalacia with cystic changes due to hypoxic-ischemic encephalopathy. We conclude that molybdenum cofactor deficiency must be included in the differential diagnosis of patients presenting with intractable seizures in the newborn period who have computed tomography and magnetic resonance imaging findings reminiscent of those of hypoxic-ischemic encephalopathy, and the urine sulfite dipstick test can be a part of the evaluation of these infants in neonatal intensive care units.

Coenzymes↗
PubMed1999

A cross-sectional study of workers in the chemical industry with occupational exposure to hexamethylenetetramine.

OBJECTIVES: To assess the health effects of hexamethylenetetramine (HMT) on the airways and the skin of workers in the chemical industry. METHODS: A cross-sectional study was performed with 17 employees of a HMT-producing chemical plant and 16 control subjects from the plant. In addition, we examined 4 out of 5 subjects who had left the production for medical reasons during the last 10 years. Anamnestic data, total and specific IgE to four environmental allergens, lung function and bronchial responsiveness to methacholine were assessed by standard procedures. Skin prick tests (SPT) and patch tests were performed with known sensitizing substances and HMT 100 mg/ml and 2% pet and aq. RESULTS: A high number of exposed subjects and controls reported symptoms during the previous year (64.7% vs 68.8%), most of them were not related to work. Work-related symptoms and objective parameters did not show differences between groups. No sensitizations to HMT as assessed by SPT or patch tests were found. Among those who had left the HMT production for medical reasons, 2 former baggers showed sensitizations to HMT by patch tests. These reported eczema during exposure but lost symptoms after removal from exposure. Geometric mean HMT concentrations as assessed by personal sampling were 0.3 [95% confidence intervals (CI) 0.1; 0.9] mg/m(3) in shiftleaders and 0.6 (95% CI 0.3; 1.1) mg/m(3) in baggers. CONCLUSION: High exposures to HMT may cause allergic contact dermatitis. There was no evidence of an increased risk for occupational asthma at mean airborne HMT concentrations below 1 mg/m(3).

Adult↗
PubMed1999

A novel protein tyrosine phosphatase gene is mutated in progressive myoclonus epilepsy of the Lafora type (EPM2).

Progressive myoclonus epilepsy of the Lafora type or Lafora disease (EPM2; McKusick no. 254780) is an autosomal recessive disorder characterized by epilepsy, myoclonus, progressive neurological deterioration and glycogen-like intracellular inclusion bodies (Lafora bodies). A gene for EPM2 previously has been mapped to chromosome 6q23-q25 using linkage analysis and homozygosity mapping. Here we report the positional cloning of the 6q EPM2 gene. A microdeletion within the EPM2 critical region, present inhomozygosis in an affected individual, was found to disrupt a novel gene encoding a putative protein tyrosine phosphatase (PTPase). The gene, denoted EPM2, presents alternative splicing in the 5' and 3' end regions. Mutational analysis revealed that EPM2 patients are homozygous for loss-of-function mutations in EPM2. These findings suggest that Lafora disease results from the mutational inactivation of a PTPase activity that may be important in the control of glycogen metabolism.

Amino Acid Sequence↗
PubMed1998

Megalencephaly and leukodystrophy with mild clinical course: a report on 12 new cases.

Twelve patients with early infancy onset megalencephaly and leukodystrophy with a mild clinical course are reported. The neuroradiological, clinical, and genetic aspects of this recently recognized familial leukodystrophy syndrome were reviewed. Five were affected siblings, and all patients had consanguineous parents. Macrocephaly, a slowly progressive delay in motor development and mild mental deterioration constitute the clinical triad of the disease, showing characteristic age-related onset. The clinical findings outlined remarkably slight functional deterioration despite severe lesions on magnetic resonance imaging (MRI), especially in the initial period. Characteristically, mental function is preserved for years after onset of the motor deficit. The MRI lesions do not reflect the progress of disease. The disease probably has an autosomal recessive mode of inheritance even though no metabolic defect has been detected to date. In a more severe variant of the mentioned disease, there is more progressive and severe neurological dysfunction, including ataxia and spastic quadriparesis, leading to an inability to walk independently after 10 years of age. In mild variants, however, disease severity varies from macrocephaly with near-normal pyschomotor development to mild motor and/or mental dysfunction. Seizures were observed in both types but response to drugs was good. The 12 patients reported here confirm the specific and distinguishing clinical and radiological features of the previously reported 51 cases with this new syndrome, while adding some information regarding identification of the disease.

Brain↗
PubMed1997

Cranial MR findings in Wilson's disease.

PURPOSE: To define various cranial MR appearances in Wilson's disease (WD). MATERIAL AND METHODS: MR examinations of 30 patients (9-44 years old) with WD were retrospectively reviewed. Six patients were asymptomatic siblings. Three other patients had isolated hepatic involvement, one with no symptoms. The remaining 21 patients had neurological involvement, 7 of whom had the mixed form of the disease. Nine patients had hepatic dysfunction, the 3 with isolated hepatic involvement and 6 of the 7 with the mixed form. RESULTS: All symptomatic patients (n = 23) had abnormal MR examinations, Atrophy was present in the majority of them. The most frequently involved sites were putamen (18/21) and pons (18/21) in patients with neurological abnormality. The putaminal lesions showed a consistent pattern of symmetric, bilateral, concentric-laminar T2 hyperintensity. Putaminal lesions were lacking in only 3 patients with neurological involvement, all of whom were relatively old and had had the disease for a longer duration. Most of the patients with hepatic dysfunction (8/9) had increased T1 signal intensity in the basal ganglia, particularly in the globus pallidus. Pontine involvement always included the dorsal aspect of the pons, however, in some cases the central portion of pons was also affected but ventrolateral longitudinal fibers were spared. Midbrain (16/21), thalamic (10/21) and caudate nucleus lesions (9/21) were also encountered. In a few patients cortical and subcortical white matter lesions were present with a predilection to the frontal lobe, particularly the precentral region. In one patient, a hemorrhagic focus was identified within the white matter lesion. CONCLUSION: On T2-weighted images, WD is suggested by: atrophy; putaminal lesions with a pattern of symmetric, bilateral, concentric-laminar T2 hyperintensity; and the involvement of the pars compacta of the substantia nigra, periaqueductal gray matter, the pontine tegmentum and the thalamus. The hepatic component of WD may cause increased T1 signal intensity in basal ganglia. In the adult age group, the basal ganglia lesions may be different from those in the pediatric group; the putaminal lesions may not be present; the globus pallidus and substantia nigra may show increased hypointensity on T2-weighted images. Cortical and subcortical lesions may also be present with a predilection to the frontal lobe.

Adolescent↗
PubMed1992

Hot water epilepsy.

The clinical and EEG features of 10 patients with hot water epilepsy were presented. Eight of the 10 cases were male. The mean age of onset was 4.7 years. In four patients partial and in six cases generalized seizures were seen. Three patients also had non-hot water precipitated seizures. Interictal EEGs showed generalized abnormalities in eight and focal abnormalities in two cases. CT was performed and found normal in two patients. Anticonvulsant therapy was instituted for all patients. In six cases with adequate follow-up, complete remission was obtained in four and the frequency of the seizures was decreased in two, with anticonvulsant therapy.

Child↗
PubMed1991

Brain death: determination with brain stem evoked potentials and radionuclide isotope studies.

Thirty-three patients fulfilling the clinical criteria for brain death were tested by Brainstem Auditory Evoked Potentials (BAEP) and Radionuclide Cerebral Angiography and Brain Perfusion Studies. There was a significant correlation between the BAEP and radionuclide study outcomes. All patients with absence of BAEP showed no cerebral perfusion. These findings, added to the clinical findings, resulted in a final diagnosis of brain death in all patients. It is concluded that BAEP and Radionuclide Cerebral Perfusion studies are useful adjuncts for proving that brain death has really occurred.

Adolescent↗