J. Colomer - Academia.edu (original) (raw)

Papers by J. Colomer

Research paper thumbnail of Severe limb girdle muscular dystrophy in Spanish gypsies: further evidence for a founder mutation in the γ-sarcoglycan gene

European Journal of Human Genetics, 1998

Limb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive muscular dystrophy with... more Limb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive muscular dystrophy with primary γ-sarcoglycan deficiency, generally associated with a severe clinical course. γ-sarcoglycan, a 35 kDa dystrophinassociated protein, is encoded by a single gene on chromosome 13q12. Six different mutations have been described in that gene, and it has been proved they are the origin of the disease. One of these mutations (C283Y), a G  A transition in codon 283, was recently and exclusively identified in Gypsy patients from different European countries. We report the study of 11 LGMD2C unrelated Gypsy families (nine Spanish and two Portugese). The muscle biopsies of these patients showed a drastically decreased immunostaining with α and γ-sarcoglycan antibodies. All the patients were homozygous for C283Y missense mutation, and all affected chromosomes (patients and heterozygous relatives) carried the allele 5 (112 bp) of the intragenic microsatellite D13S232. Unexpectedly, this allele is most frequent in the Caucasian population but not in the normal Gypsy population. The clinical severity of all patients demonstrates that the C283Y missense mutation in a homozygous state causes a severe LGMD2C (DMD-like). The elevated number of families ascertained let us assume that LGMD2C is prevalent in the Gypsy population, and that all the families have inherited a founding mutation.

Research paper thumbnail of Long-term improvement of slow-channel congenital myasthenic syndrome with fluoxetine

Neuromuscular Disorders, 2006

We report on a 15-year-old patient who was diagnosed with congenital myasthenic syndrome (CMS) at... more We report on a 15-year-old patient who was diagnosed with congenital myasthenic syndrome (CMS) at the age of 7 months. At initial diagnosis, the CMS was not further characterized. The patient was treated for several years with the anticholinesterase drug (Mestinon), without clinical benefit. The patient deteriorated progressively and became dependent on home nocturnal ventilatory support, being unable to take part in daily life activities at age of 12 years. At age 14, the slow-channel syndrome mutation CHRNE L269F (805C>T) was detected and acetylcholinesterase inhibitor therapy was immediately stopped. Fluoxetine therapy was started and gradually increased over 2 months. The boy improved dramatically in strength and endurance and was taken off ventilatory support 1 month after the fluoxetine therapy was initiated. The clinical improvement was confirmed by functional respiratory and electrophysiological tests.

Research paper thumbnail of Moyamoya Syndrome Associated With Down Syndrome: Outcome After Surgical Revascularization

Pediatrics, 2005

Objectives. This study was undertaken to describe the clinical, radiologic, and angiographic feat... more Objectives. This study was undertaken to describe the clinical, radiologic, and angiographic features of moyamoya syndrome in a surgical series of children and adults with Down syndrome. We wished to define the features of moyamoya syndrome associated with Down syndrome and to determine the results of surgical revascularization among these patients at early and late follow-up times. Methods. We reviewed the clinical, radiologic, and angiographic records of all patients with moyamoya syndrome associated with Down syndrome, as a subset of a previously reported, consecutive series of patients who underwent cerebral revascularization surgery with a standardized surgical procedure, pial synangiosis, between January 1, 1985, and June 30, 2004. Results. Of 181 patients with moyamoya syndrome from the initial series who were treated surgically during the study period, 16 patients had Down syndrome (10 female patients and 6 male patients). The average age at onset was 9.3 years (range: 1–29 ...

Research paper thumbnail of Severe mental retardation in a young boy with an in-frame deletion in the dystrophin gene

European Journal of Pediatrics, 1994

We report here a mentally retarded 32-month-old boy whose initial diagnosis was A n g e l m a n s... more We report here a mentally retarded 32-month-old boy whose initial diagnosis was A n g e l m a n syndrome based on his clinical features. Cytogenetic studies showed a normal karyotype. Due to an elevated level of serum creatine kinase activity, we performed analyses to rule out a myopathic process. Although the electromyogram was normal, a few scattered necrotic fibres were seen in the muscle biopsy. D N A and dystrophin studies revealed an in-frame deletion in the 5" region of the dystrophin gene and an abnormal form of the protein product, consistent with a diagnosis of dystrophinopathy. We cannot totally rule out the possibility that this boy has the two separate conditions. K e y w o r d s Dystrophinopathy Dystrophin 9 Mental retardation Abrcviations AS A n g e l m a n syndrome 9 BMD Becker muscular dystrophy 9 CK creatine kinase DMD Duchenne muscular dystrophy

Research paper thumbnail of Hereditary motor and sensory neuropathy-Lom (HMSNL) in an Italian gypsy family

Neuromuscular Disorders, 1997

Hereditary motor and sensory neuropathy type Lom, initially identified in Roma (Gypsy) families f... more Hereditary motor and sensory neuropathy type Lom, initially identified in Roma (Gypsy) families from Bulgaria, has been mapped to 8q24. Further refined mapping of the region has been undertaken on DNA from patients diagnosed across Europe. The refined map consists of 25 microsatellite markers over approximately 3 cM. In this collaborative study we have identified a number of historical recombinations resulting from the spread of the hereditary motor and sensory neuropathy type Lom gene through Europe with the migration and isolation of Gypsy groups. Recombination mapping and the minimal region of homozygosity reduced the original 3 cM hereditary motor and sensory neuropathy type Lom region to a critical interval of about 200 kb.

Research paper thumbnail of Inborn errors of metabolism and motor disturbances in children

Journal of Inherited Metabolic Disease, 2009

Research paper thumbnail of Clinical and molecular genetic findings in COLQ-mutant congenital myasthenic syndromes

Research paper thumbnail of Clinical and molecular genetic findings in COLQ-mutant congenital myasthenic syndromes

Research paper thumbnail of Phenotypical spectrum of DOK7 mutations in congenital myasthenic syndromes

Brain, 2007

Dok ('downstream-of-kinase') family of cytoplasmic proteins play a role in signalling downstream ... more Dok ('downstream-of-kinase') family of cytoplasmic proteins play a role in signalling downstream of receptor and non-receptor phosphotyrosine kinases. Recently, a skeletal muscle receptor tyrosine kinase (MuSK)-interacting cytoplasmic protein termed Dok-7 has been identified. Subsequently, we and others identified mutations in DOK7 as a cause of congenital myasthenic syndromes (CMS), providing evidence for a crucial role of Dok-7 in maintaining synaptic structure. Here we present clinical and molecular genetic data of 14 patients from 12 independent kinships with 13 different mutations in the DOK7 gene.The clinical picture of CMS with DOK7 mutations is highly variable.The age of onset may vary between birth and the third decade. However, most of the patients display a characteristic 'limb-girdle' pattern of weakness with a waddling gait and ptosis, but without ophthalmoparesis. Respiratory problems were frequent. Patients did not benefit from long-term therapy with esterase inhibitors; some of the patients even worsened. DOK7 mutations have emerged as one of the major genetic defects in CMS. The clinical picture differs significantly from CMS caused by mutations in other genes, such as the acetylcholine receptor (AChR) subunit genes. None of the patients with DOK7 mutations had tubular aggregates in the muscle biopsy, implying that 'limb-girdle myasthenia (LGM) with tubular aggregates' previously described in literature may be a pathogenic entity distinct from CMS caused by DOK7 mutations.

Research paper thumbnail of Severe limb girdle muscular dystrophy in Spanish gypsies: further evidence for a founder mutation in the γ-sarcoglycan gene

European Journal of Human Genetics, 1998

Limb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive muscular dystrophy with... more Limb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive muscular dystrophy with primary γ-sarcoglycan deficiency, generally associated with a severe clinical course. γ-sarcoglycan, a 35 kDa dystrophinassociated protein, is encoded by a single gene on chromosome 13q12. Six different mutations have been described in that gene, and it has been proved they are the origin of the disease. One of these mutations (C283Y), a G  A transition in codon 283, was recently and exclusively identified in Gypsy patients from different European countries. We report the study of 11 LGMD2C unrelated Gypsy families (nine Spanish and two Portugese). The muscle biopsies of these patients showed a drastically decreased immunostaining with α and γ-sarcoglycan antibodies. All the patients were homozygous for C283Y missense mutation, and all affected chromosomes (patients and heterozygous relatives) carried the allele 5 (112 bp) of the intragenic microsatellite D13S232. Unexpectedly, this allele is most frequent in the Caucasian population but not in the normal Gypsy population. The clinical severity of all patients demonstrates that the C283Y missense mutation in a homozygous state causes a severe LGMD2C (DMD-like). The elevated number of families ascertained let us assume that LGMD2C is prevalent in the Gypsy population, and that all the families have inherited a founding mutation.

Research paper thumbnail of Long-term improvement of slow-channel congenital myasthenic syndrome with fluoxetine

Neuromuscular Disorders, 2006

We report on a 15-year-old patient who was diagnosed with congenital myasthenic syndrome (CMS) at... more We report on a 15-year-old patient who was diagnosed with congenital myasthenic syndrome (CMS) at the age of 7 months. At initial diagnosis, the CMS was not further characterized. The patient was treated for several years with the anticholinesterase drug (Mestinon), without clinical benefit. The patient deteriorated progressively and became dependent on home nocturnal ventilatory support, being unable to take part in daily life activities at age of 12 years. At age 14, the slow-channel syndrome mutation CHRNE L269F (805C>T) was detected and acetylcholinesterase inhibitor therapy was immediately stopped. Fluoxetine therapy was started and gradually increased over 2 months. The boy improved dramatically in strength and endurance and was taken off ventilatory support 1 month after the fluoxetine therapy was initiated. The clinical improvement was confirmed by functional respiratory and electrophysiological tests.

Research paper thumbnail of Moyamoya Syndrome Associated With Down Syndrome: Outcome After Surgical Revascularization

Pediatrics, 2005

Objectives. This study was undertaken to describe the clinical, radiologic, and angiographic feat... more Objectives. This study was undertaken to describe the clinical, radiologic, and angiographic features of moyamoya syndrome in a surgical series of children and adults with Down syndrome. We wished to define the features of moyamoya syndrome associated with Down syndrome and to determine the results of surgical revascularization among these patients at early and late follow-up times. Methods. We reviewed the clinical, radiologic, and angiographic records of all patients with moyamoya syndrome associated with Down syndrome, as a subset of a previously reported, consecutive series of patients who underwent cerebral revascularization surgery with a standardized surgical procedure, pial synangiosis, between January 1, 1985, and June 30, 2004. Results. Of 181 patients with moyamoya syndrome from the initial series who were treated surgically during the study period, 16 patients had Down syndrome (10 female patients and 6 male patients). The average age at onset was 9.3 years (range: 1–29 ...

Research paper thumbnail of Severe mental retardation in a young boy with an in-frame deletion in the dystrophin gene

European Journal of Pediatrics, 1994

We report here a mentally retarded 32-month-old boy whose initial diagnosis was A n g e l m a n s... more We report here a mentally retarded 32-month-old boy whose initial diagnosis was A n g e l m a n syndrome based on his clinical features. Cytogenetic studies showed a normal karyotype. Due to an elevated level of serum creatine kinase activity, we performed analyses to rule out a myopathic process. Although the electromyogram was normal, a few scattered necrotic fibres were seen in the muscle biopsy. D N A and dystrophin studies revealed an in-frame deletion in the 5" region of the dystrophin gene and an abnormal form of the protein product, consistent with a diagnosis of dystrophinopathy. We cannot totally rule out the possibility that this boy has the two separate conditions. K e y w o r d s Dystrophinopathy Dystrophin 9 Mental retardation Abrcviations AS A n g e l m a n syndrome 9 BMD Becker muscular dystrophy 9 CK creatine kinase DMD Duchenne muscular dystrophy

Research paper thumbnail of Hereditary motor and sensory neuropathy-Lom (HMSNL) in an Italian gypsy family

Neuromuscular Disorders, 1997

Hereditary motor and sensory neuropathy type Lom, initially identified in Roma (Gypsy) families f... more Hereditary motor and sensory neuropathy type Lom, initially identified in Roma (Gypsy) families from Bulgaria, has been mapped to 8q24. Further refined mapping of the region has been undertaken on DNA from patients diagnosed across Europe. The refined map consists of 25 microsatellite markers over approximately 3 cM. In this collaborative study we have identified a number of historical recombinations resulting from the spread of the hereditary motor and sensory neuropathy type Lom gene through Europe with the migration and isolation of Gypsy groups. Recombination mapping and the minimal region of homozygosity reduced the original 3 cM hereditary motor and sensory neuropathy type Lom region to a critical interval of about 200 kb.

Research paper thumbnail of Inborn errors of metabolism and motor disturbances in children

Journal of Inherited Metabolic Disease, 2009

Research paper thumbnail of Clinical and molecular genetic findings in COLQ-mutant congenital myasthenic syndromes

Research paper thumbnail of Clinical and molecular genetic findings in COLQ-mutant congenital myasthenic syndromes

Research paper thumbnail of Phenotypical spectrum of DOK7 mutations in congenital myasthenic syndromes

Brain, 2007

Dok ('downstream-of-kinase') family of cytoplasmic proteins play a role in signalling downstream ... more Dok ('downstream-of-kinase') family of cytoplasmic proteins play a role in signalling downstream of receptor and non-receptor phosphotyrosine kinases. Recently, a skeletal muscle receptor tyrosine kinase (MuSK)-interacting cytoplasmic protein termed Dok-7 has been identified. Subsequently, we and others identified mutations in DOK7 as a cause of congenital myasthenic syndromes (CMS), providing evidence for a crucial role of Dok-7 in maintaining synaptic structure. Here we present clinical and molecular genetic data of 14 patients from 12 independent kinships with 13 different mutations in the DOK7 gene.The clinical picture of CMS with DOK7 mutations is highly variable.The age of onset may vary between birth and the third decade. However, most of the patients display a characteristic 'limb-girdle' pattern of weakness with a waddling gait and ptosis, but without ophthalmoparesis. Respiratory problems were frequent. Patients did not benefit from long-term therapy with esterase inhibitors; some of the patients even worsened. DOK7 mutations have emerged as one of the major genetic defects in CMS. The clinical picture differs significantly from CMS caused by mutations in other genes, such as the acetylcholine receptor (AChR) subunit genes. None of the patients with DOK7 mutations had tubular aggregates in the muscle biopsy, implying that 'limb-girdle myasthenia (LGM) with tubular aggregates' previously described in literature may be a pathogenic entity distinct from CMS caused by DOK7 mutations.