Calpainopathy-a survey of mutations and polymorphisms.

Limb-girdle muscular dystrophy type 2A (LGMD2A) is an autosomal recessive disorder characterized mainly by symmetrical and selective atrophy of the proximal limb muscles. It derives from defects in the human CAPN3 gene, which encodes the skeletal muscle-specific member of the calpain family. This report represents a compilation of the mutations and variants identified so far in this gene.

Deletion analysis in Turkish patients with spinal muscular atrophy.

Childhood proximal spinal muscular atrophy (SMA) is an autosomal recessive disorder which presents as a severe, intermediate or mild condition. Here we present the molecular analysis of SMA candidate genes, the survival motor neuron gene (SMN), the neuronal apoptosis inhibitory protein gene (NAIP) and the p44 gene. Deletion frequency rate of these candidate genes is 93% in 106 Turkish SMA patients.

Acute disseminated encephalomyelitis in childhood: report of 10 cases.

We report 10 children with the diagnosis of acute disseminated encephalomyelitis. Diagnosis was based on clinical and radiologic findings, and after acute encephalitis was excluded by negative culture and antibody results. The most common presenting symptom was ataxia, followed by optic neuropathy, cranial nerve palsy, convulsions, motor dysfunction, and loss of consciousness.

Assignment of the muscle-eye-brain disease gene to 1p32-p34 by linkage analysis and homozygosity mapping.

Muscle-eye-brain disease (MEB) is an autosomal recessive disease of unknown etiology characterized by severe mental retardation, ocular abnormalities, congenital muscular dystrophy, and a polymicrogyria-pachygyria-type neuronal migration disorder of the brain. A similar combination of muscle and brain involvement is also seen in Walker-Warburg syndrome (WWS) and Fukuyama congenital muscular dystrophy (FCMD). Whereas the gene underlying FCMD has been mapped and cloned, the genetic location of the WWS gene is still unknown.

Efficacy of transurethral electrovaporization of the prostate with respect to standard transurethral resection.

Transurethral electrovaporization of the prostate (TVP) has been introduced as an alternative to standard transurethral resection of the prostate (TURP) with lesser morbidity. However, the efficacy of this new technique has not been well known. To compare the results of standard TURP and TVP, 76 patients with symptomatic benign prostatic hyperplasia (BFH) were divided into two groups in a randomized clinical trial.

Prenatal diagnosis of limb-girdle muscular dystrophy type 2C.

After studies which have mapped the gamma-sarcoglycan deficient limb-girdle muscular dystrophy (LGMD2C) to chromosome 13q12 and recent identification of mutations within this gene, prenatal diagnosis has become possible. The deletion of exon 5 in the gamma-sarcoglycan gene was found in a consanguineous family and prenatal diagnosis was successfully provided. This is the first prenatal diagnosis of LGMD2C.

DNA diagnostic tests in Xp21 dystrophy families for prenatal diagnosis.

Duchenne and Becker muscular dystrophies are X-linked genetic disorders characterized by dystrophin gene defects. We have studied 250 families with Duchenne and Becker muscular dystrophies (D/BMD) by molecular genetic methods since 1992. Nineteen exons of the dystrophin gene were analyzed for deletion.

Clinical observations in autosomal recessive spastic paraplegia in childhood and further evidence for genetic heterogeneity.

Among our 23 families (32 cases) with autosomal recessive hereditary spastic paraplegia (AR-HSP) all presenting in childhood, 9 families had the "pure" form. Occasional patients with this form had upper extremity hyperreflexia, pes cavus and sphincter disturbances, even at the early stages. Fourteen families were classified as the "complicated" types which manifested with mental retardation and cerebellar abnormalities.

mtDNA nt3243 mutation, external ophthalmoplegia, and hypogonadism in an adolescent girl.

A 14-year-old girl presented with a 3-month history of easy fatigue and exercise intolerance, especially when climbing stairs. She had a mild ptosis and mild limitation of upward gaze. Her puberty was delayed, and she manifested hypogonadotrophic hypogonadism.

Merosin-deficient congenital muscular dystrophy with severe mental retardation and normal cranial MRI: a report of two siblings.

The evidence of severe structural brain abnormalities in association with severe mental retardation is characteristic in congenital muscular dystrophy (CMD) forms other than the 'classical' form. However, it seems that the nosology of CMD is not complete yet, as we have clinical, immunohistochemical and genetic data suggesting that there are other unclassified forms. Here we report two CMD siblings from a consanguineous family with partial merosin-deficiency in muscle biopsies, severe mental retardation and normal MRI of the brain.

Identification of a new locus for a peculiar form of congenital muscular dystrophy with early rigidity of the spine, on chromosome 1p35-36.

Classical congenital muscular dystrophies (CMDs) are autosomal recessive neuromuscular disorders characterized by early onset of hypotonia and weakness, atrophy of limbs and trunk muscles, contractures, and dystrophic changes in the muscle biopsy. So far, only one gene, LAMA2 (6q2), which encodes the laminin alpha2 chain (or merosin), has been identified in these disorders. Mutations in LAMA2 cause CMD with complete or partial merosin deficiency, detectable by immunocytochemistry on muscle biopsies, and account for approximately 50% of CMD cases.

PCR based mutation screening of the laminin alpha2 chain gene (LAMA2): application to prenatal diagnosis and search for founder effects in congenital muscular dystrophy.

Classical congenital muscular dystrophy with merosin deficiency is caused by mutations in the laminin alpha2 chain gene (LAMA2). Extended sequencing of the introns flanking the 64 LAMA2 exons was carried out and, based on these sequences, oligonucleotide primers were designed to amplify the coding region of each exon separately. By PCR-SSCP analysis, we identified eight new mutations in nine families originating from various countries.

Allele distribution of D5S125, MAP1B5' and D5S679 microsatellite markers in Turkish spinal muscular atrophy families.

Spinal muscular atrophy (SMA) is an autosomal recessive disease and one of the most common genetic causes of death in childhood. The gene for SMA has been mapped to chromosome 5q11.2-13.

Cerebral infarct associated with factor V Leiden mutation in a boy with hemophilia A.

An 11-year-old boy with mild hemophilia A was admitted to our hospital because of focal convulsions. Magnetic resonance imaging showed an old occipital infarct. Protein C, S, antithrombin III, anticardiolipin antibodies and fibrinogen were normal.

Calpain-3 deficiency causes a mild muscular dystrophy in childhood.

Among our 20 families with LGMD2, 10 were documented to have muscle-specific calcium-activated neutral protease 3 (calpain-3) deficiency. Consanguinity was present in all. The current ages of the index cases were between 12 and 23 years, and there were additional nine members affected.

A biochemical, genetic, and clinical survey of autosomal recessive limb girdle muscular dystrophies in Turkey.

Autosomal recessive limb girdle muscular dystrophy (LGMD2) is a clinically and genetically heterogenous group of diseases involving at least six different loci. Five genes have already been identified: calpain-3 at LGMD2A (15q15), and four members of the sarcoglycan (SG) complex, alpha-SG at LGMD2D (17q21), beta-SG at LGMD2E (4q12), gamma-SG at LGMD2C (13q12), and delta-SG at LGMD2F (5q33-q34). The gene product at LGMD2B (2p13-p16) is still unknown and at least one other gene is still unmapped.

Correlation of laboratory and clinical findings with the location of Xp21 deletion in Duchenne muscular dystrophy.

Laboratory and clinical features of 28 Duchenne muscular dystrophy patients were evaluated. Positive family history was present in only two cases (7.1%).

Genetics of laminin alpha 2 chain (or merosin) deficient congenital muscular dystrophy: from identification of mutations to prenatal diagnosis.

Congenital muscular dystrophies (CMD) are a clinically and genetically heterogeneous group of muscle disorders, with autosomal recessive inheritance. Absence of the laminin alpha 2 chain in the skeletal muscle of patients with classical CMD has permitted the identification of a subgroup, referred to as 'merosin-deficient CMD or laminin alpha 2 chain deficient CMD'. We first identified a nonsense and a splice site mutation in laminin alpha 2 gene (LAMA2) (Glu1241 stop, 4573-2A-->T).

Prenatal diagnosis in merosin-deficient congenital muscular dystrophy.

Prenatal diagnosis was carried out in five merosin-deficient congenital muscular dystrophy (CMD) families. We studied both laminin-alpha 2 chain expression in trophoblast using immunocytochemistry and linkage analysis to the LAMA2 locus. In four families there was good agreement between the immunocytochemistry and linkage analysis results: in one case the trophoblast was negative for LAMA2 expression and haplotype analysis suggested the foetus was affected; in the other three cases the laminin-alpha 2 chain expression was normal and foetuses were found to be carriers.

Multiple independent molecular etiology for limb-girdle muscular dystrophy type 2A patients from various geographical origins.

Limb-girdle muscular dystrophies (LGMDs) are a group of neuromuscular diseases presenting great clinical heterogeneity. Mutations in CANP3, the gene encoding muscle-specific calpain, were used to identify this gene as the genetic site responsible for autosomal recessive LGMD type 2A (LGMD2A; MIM 253600). Analyses of the segregation of markers flanking the LGMD2A locus and a search for CANP3 mutations were performed for 21 LGMD2 pedigrees from various origins.

The role of immunocytochemistry and linkage analysis in the prenatal diagnosis of merosin-deficient congenital muscular dystrophy.

Complete or partial deficiency of the laminin alpha2 chain of merosin has been demonstrated in a proportion of children with classical congenital muscular dystrophy and linkage to the laminin alpha2 chain gene (LAMA2) on chromosome 6q2 has been established. As the laminin alpha2 chain is also expressed in the trophoblast, its detection and linkage analysis are useful tools for prenatal diagnosis. We report our experience of seven prenatal diagnoses in families with partial deficiency or total absence of the laminin alpha2 chain in the muscle of the propositi.

Late onset muscular dystrophy with cerebral white matter changes due to partial merosin deficiency.

Merosin-deficient congenital muscular dystrophy (CMD) is an autosomal recessive condition usually with onset at birth or within the first months of life. Affected children are severely disabled and usually do not achieve the ability to walk without support. They invariably have white matter abnormalities on brain magnetic resonance imaging (MRI).

Refinement of the laminin alpha2 chain locus to human chromosome 6q2 in severe and mild merosin deficient congenital muscular dystrophy.

About half of the children with classical congenital muscular dystrophy (CMD) show an absence in their skeletal muscle of laminin alpha2 chain, one of the components of the extracellular matrix protein, merosin. Linkage analysis implicated the laminin alpha2 chain gene (LAMA2) on chromosome 6q2, now confirmed by the discovery of mutations in the laminin alpha2 chain gene. We have further investigated the location of the LAMA2 locus on chromosome 6q2, using both linkage analysis in nine informative families and homozygosity mapping in 13 consanguineous families.