RESUMO
By clinical whole exome sequencing, we identified 12 individuals with ages 3 to 37 years, including three individuals from the same family, with a consistent phenotype of intellectual disability (ID), macrocephaly, and overgrowth of adenoid tissue. All 12 individuals harbored a rare heterozygous variant in ZBTB7A which encodes the transcription factor Zinc finger and BTB-domain containing protein 7A, known to play a role in lympho- and hematopoiesis. ID was generally mild. Fetal hemoglobin (HbF) fraction was elevated 2.2%-11.2% (reference value <2% in individuals > 6 months) in four of the five individuals for whom results were available. Ten of twelve individuals had undergone surgery at least once for lymphoid hypertrophy limited to the pharynx. In the most severely affected individual (individual 1), airway obstruction resulted in 17 surgical procedures before the age of 13 years. Sleep apnea was present in 8 of 10 individuals. In the nine unrelated individuals, ZBTB7A variants were novel and de novo. The six frameshift/nonsense and four missense variants were spread throughout the gene. This is the first report of a cohort of individuals with this novel syndromic neurodevelopmental disorder.
Assuntos
Deficiência Intelectual , Megalencefalia , Transtornos do Neurodesenvolvimento , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Hemoglobina Fetal , Humanos , Deficiência Intelectual/genética , Tecido Linfoide , Megalencefalia/genética , Transtornos do Neurodesenvolvimento/genética , Fatores de Transcrição/genéticaRESUMO
OBJECTIVE: To evaluate the automated determination of total cerebrospinal fluid (CSF) folates for the diagnosis of cerebral folate deficiency. METHOD: CSF and serum samples were analyzed in 60 children with different neurological disorders. RESULT: In all patients with genetic conditions leading to profound cerebral folate deficiency (impaired folate transport and metabolism), the automated folate determination showed altered values. CONCLUSION: CSF folate quantification provided profound CSF folate deficiency diagnosis caused either by folate transport or metabolism deficiencies.