RESUMO
Warburg Micro syndrome (WARBM1) is a severe autosomal recessive disorder characterized by developmental abnormalities of the eye and central nervous system and by microgenitalia. We identified homozygous inactivating mutations in RAB3GAP, encoding RAB3 GTPase activating protein, a key regulator of the Rab3 pathway implicated in exocytic release of neurotransmitters and hormones, in 12 families with Micro syndrome. We hypothesize that the underlying pathogenesis of Micro syndrome is a failure of exocytic release of ocular and neurodevelopmental trophic factors.
Assuntos
Mutação , Proteínas rab de Ligação ao GTP/metabolismo , Domínio Catalítico , Sistema Nervoso Central/anormalidades , Anormalidades do Olho/patologia , Genitália/anormalidades , Humanos , Dados de Sequência Molecular , Síndrome , Proteínas rab de Ligação ao GTP/genéticaRESUMO
PURPOSE: To present a boy with unilateral duplication of the eye. METHOD: The case history is described from the first visit at birth to the age of 14 years. RESULTS: A review of the literature shows that this malformation is compatible with life although malformations of the brain and epilepsy have been reported in all cases where a paediatric exam was described. We show that the malformation can appear as a synophthalmic eye in a single orbit or as two separate unilateral eyes in a separate orbit. CONCLUSION: We find the denomination, triophthalmia insufficient to differentiate between the two types and suggest a differentiation between unilateral synophthalmia and ipsilateral ocular duplication.
Assuntos
Anormalidades do Olho/patologia , Adulto , Feminino , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , MasculinoRESUMO
A 20-year-old Caucasian male with mild Noonan phenotype associated with coloboma of the iris and choroid is described. It is concluded that iris and retinal colobomas could be a rare feature of Noonan sydrome.
Assuntos
Corioide/anormalidades , Coloboma/patologia , Iris/anormalidades , Síndrome de Noonan/patologia , Adulto , Humanos , Masculino , FenótipoRESUMO
We report on a patient with blepharophimosis who after unsuccessful surgery developed progressive corneal vascularization. The patient had conductive hearing loss, acroosteolysis of the phalanges, arthropathy, loss of subcutaneous fat of the hands, feet and face, and oligospermia. He had had spontaneous pneumothorax four times. We have found no similar case reports in the literature and suggest that this is a new syndrome, which must be differentiated from hereditary mucoepithelial dysplasia, mandibuloacral dysplasia, keratitis-ichthyosis-deafness syndrome, Hajdu-Cheney syndrome, Penttinen syndrome, and mucopolysaccharidoses.
Assuntos
Acro-Osteólise/complicações , Blefarofimose/complicações , Neovascularização da Córnea/complicações , Perda Auditiva Condutiva/complicações , Acro-Osteólise/genética , Adulto , Blefarofimose/genética , Tecido Conjuntivo/patologia , Neovascularização da Córnea/genética , Anormalidades Craniofaciais/complicações , Anormalidades Craniofaciais/genética , Diagnóstico Diferencial , Displasia Ectodérmica/complicações , Displasia Ectodérmica/genética , Perda Auditiva Condutiva/genética , Humanos , Masculino , Oligospermia/complicações , Oligospermia/genética , Sindactilia/complicações , Sindactilia/genética , SíndromeRESUMO
Cohen syndrome is an uncommon autosomal recessive disorder whose diagnosis is based on the clinical picture of nonprogressive psychomotor retardation and microcephaly, characteristic facial features, retinal dystrophy, and intermittent neutropenia. We have refined the critical region on chromosome 8q22 by haplotype analysis, and we report the characterization of a novel gene, COH1, that is mutated in patients with Cohen syndrome. The longest transcript (14,093 bp) is widely expressed and is transcribed from 62 exons that span a genomic region of approximately 864 kb. COH1 encodes a putative transmembrane protein of 4,022 amino acids, with a complex domain structure. Homology to the Saccharomyces cerevisiae VPS13 protein suggests a role for COH1 in vesicle-mediated sorting and transport of proteins within the cell.
Assuntos
Anormalidades Múltiplas/genética , Mutação , Anormalidades Múltiplas/patologia , Adulto , Criança , Cromossomos Humanos Par 8 , Estudos de Coortes , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/patologia , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/patologia , Feminino , Humanos , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Masculino , Proteínas de Membrana/genética , Microcefalia/genética , Microcefalia/patologia , Dados de Sequência Molecular , Homologia de Sequência de Aminoácidos , Síndrome , Proteínas de Transporte VesicularRESUMO
Cohen syndrome is an autosomal recessive condition associated with developmental delay, facial dysmorphism, pigmentary retinopathy, and neutropenia. The pleiotropic phenotype, combined with insufficient clinical data, often leads to an erroneous diagnosis and has led to confusion in the literature. Here, we report the results of a comprehensive genotype-phenotype study on the largest cohort of patients with Cohen syndrome assembled to date. We found 22 different COH1 mutations, of which 19 are novel, in probands identified by our diagnostic criteria. In addition, we identified another three novel mutations in patients with incomplete clinical data. By contrast, no COH1 mutations were found in patients with a provisional diagnosis of Cohen syndrome who did not fulfill the diagnostic criteria ("Cohen-like" syndrome). This study provides a molecular confirmation of the clinical phenotype associated with Cohen syndrome and provides a basis for laboratory screening that will be valuable in its diagnosis.