Assuntos
DNA Ligase Dependente de ATP/deficiência , Síndromes de Imunodeficiência/genética , Criança , Pré-Escolar , DNA Ligase Dependente de ATP/genética , Diagnóstico Diferencial , Feminino , Genótipo , Humanos , Síndromes de Imunodeficiência/diagnóstico , Lactente , Recém-Nascido , Masculino , MutaçãoRESUMO
Heimler syndrome (HS) is a rare recessive disorder characterized by sensorineural hearing loss (SNHL), amelogenesis imperfecta, nail abnormalities, and occasional or late-onset retinal pigmentation. It is the mildest form known to date of peroxisome biogenesis disorder caused by hypomorphic mutations of PEX1 and PEX6 genes. We report on a second Moroccan family with Heimler syndrome with early onset, severe visual impairment and important phenotypic overlap with Usher syndrome. The patient carried a novel homozygous missense variant c.3140T > C (p.Leu1047Pro) of PEX1 gene. As standard biochemical screening of blood for evidence of a peroxisomal disorder did not provide a diagnosis in the individuals with HS, patients with SNHL and retinal pigmentation should have mutation analysis of PEX1 and PEX6 genes.
Assuntos
Adenosina Trifosfatases/genética , Amelogênese Imperfeita/genética , Perda Auditiva Neurossensorial/genética , Proteínas de Membrana/genética , Unhas Malformadas/genética , Retinose Pigmentar/genética , ATPases Associadas a Diversas Atividades Celulares , Amelogênese Imperfeita/complicações , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Perda Auditiva Neurossensorial/complicações , Perda Auditiva Neurossensorial/fisiopatologia , Homozigoto , Humanos , Masculino , Mutação , Unhas Malformadas/complicações , Linhagem , Transtornos Peroxissômicos/genética , Transtornos Peroxissômicos/fisiopatologia , Fenótipo , Retinose Pigmentar/complicações , Retinose Pigmentar/fisiopatologiaRESUMO
Raine syndrome is a rare autosomal recessive bone dysplasia characterized by characteristic facial features with exophthalmos and generalized osteosclerosis. Amelogenesis imperfecta, hearing loss, seizures, and intracerebral calcification are apparent in some affected individuals. Originally, Raine syndrome was originally reported as a lethal syndrome. However, recently a milder phenotype, compatible with life, has been described. Biallelic variants inFAM20C, encoding aGolgi casein kinase involved in biomineralisation, have been identified in affected individuals. We report here a consanguineous Moroccan family with two affected siblingsa girl aged 18 and a boy of 15years. Clinical features, including learning disability, seizures and amelogenesis imperfecta, initially suggested a diagnosis of Kohlschutter-Tonz syndrome. However,a novel homozygous FAM20Cvariantc.676T > A, p.(Trp226Arg) was identified in the affected siblings. Our report reinforces that Raine syndrome is compatible with life, and that mild hypophosphatemia and amelogenesis imperfecta are key features of the attenuated form.