RESUMO
PURPOSE: To define the clinical characteristics of patients with variants in TCF20, we describe 27 patients, 26 of whom were identified via exome sequencing. We compare detailed clinical data with 17 previously reported patients. METHODS: Patients were ascertained through molecular testing laboratories performing exome sequencing (and other testing) with orthogonal confirmation; collaborating referring clinicians provided detailed clinical information. RESULTS: The cohort of 27 patients all had novel variants, and ranged in age from 2 to 68 years. All had developmental delay/intellectual disability. Autism spectrum disorders/autistic features were reported in 69%, attention disorders or hyperactivity in 67%, craniofacial features (no recognizable facial gestalt) in 67%, structural brain anomalies in 24%, and seizures in 12%. Additional features affecting various organ systems were described in 93%. In a majority of patients, we did not observe previously reported findings of postnatal overgrowth or craniosynostosis, in comparison with earlier reports. CONCLUSION: We provide valuable data regarding the prognosis and clinical manifestations of patients with variants in TCF20.
Assuntos
Transtorno do Espectro Autista/genética , Deficiência Intelectual/genética , Transtornos do Neurodesenvolvimento/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Idoso , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/patologia , Criança , Pré-Escolar , Exoma/genética , Feminino , Humanos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/patologia , Sequenciamento do Exoma , Adulto JovemRESUMO
Disorders of intracellular cobalamin (vitamin B12) metabolism result from deficient synthesis of the coenzymes derived from vitamin B12: adenosylcobalamin and methylcobalamin. Disturbances of cobalamin-cofactor synthesis result in elevated levels of homocysteine and/or methylmalonic acid. Nine defects of intracellular cobalamin metabolism have been defined. The most common of these disorders is cblC (combined methylmalonic aciduria and homocystinuria). The cblD disorder is rare with fewer than twenty cases reported in the literature. Some cblD patients have combined methylmalonic aciduria and homocystinuria (referred to as "cblD original," "cblD-combined," or herein "cblD-MMA/HC"); some have isolated homocystinuria (referred to as "cblD-variant 1" or herein "cblD-HC"); and others have isolated methylmalonic aciduria (called "cblD-variant 2" or herein "cblD-MMA"). Only six cases of cblD-HC have been defined thus far. We report the 7th case of cblD-HC. The clinical manifestations, biochemical profile, genetic mutation, and plausible ancestry are discussed.