Asunto(s)
Acetazolamida/uso terapéutico , Apnea/tratamiento farmacológico , Hiperventilación/tratamiento farmacológico , Discapacidad Intelectual/tratamiento farmacológico , Niño , Facies , Humanos , Hiperventilación/genética , Hiperventilación/patología , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Masculino , Adulto JovenRESUMEN
BACKGROUND: Mutations in the TUBA1A gene have been reported in patients with lissencephaly and perisylvian pachygyria. METHODS: Twenty-five patients with malformations of cortical development ranging from lissencephaly to polymicrogyria were screened for mutations in TUBA1A. RESULTS: Two novel heterozygous missense mutations in TUBA1A were identified: c.629A>G (p.Tyr210Cys) occurring de novo in a boy with lissencephaly, and c.13A>C (p.Ile5Leu) affecting 2 sisters with polymicrogyria whose mother presented somatic mosaicism for the mutation. CONCLUSIONS: Mutations in TUBA1A have been described in patients with lissencephaly and pachygyria. We report a mutation in TUBA1A as a cause of polymicrogyria. So far, all mutations in TUBA1A have occurred de novo, resulting in isolated cases. This article describes familial recurrence of TUBA1A mutations due to somatic mosaicism in a parent. These findings broaden the phenotypic spectrum associated with TUBA1A mutations and have implications for genetic counseling.