Maternal mosaicism underlies the inheritance of a rare germline AKT3 variant which is responsible for megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome in two Roma half-siblings.
Exp Mol Pathol
; 115: 104471, 2020 08.
Article
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| MEDLINE
| ID: mdl-32446860
ABSTRACT
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome is a developmental brain disorder characterized by an enlarged brain size with bilateral perisylvian polymicrogyria and a variable degree of ventriculomegaly. MPPH syndrome is associated with oromotor dysfunction, epilepsy, intellectual disability and postaxial hexadactyly. The molecular diagnosis of this disorder is established by the identification of a pathogenic variant in either AKT3, CCND2 or PIK3R2. Previously reported AKT3 variants are associated with various brain abnormalities and may lead to megalencephaly. MPPH syndrome is usually due to germline pathogenic AKT3 variants. Somatic mosaic pathogenic variants associated with hemimegalencephaly, which is similar to MPPH, have also been observed. A Hungarian Roma family with two half-siblings, which present with intellectual disability, dysmorphic features, epilepsy, brain malformations, and megalencephaly was studied. Whole exome sequencing (WES) analysis was performed. WES analysis revealed a heterozygous c.1393C > T p.(Arg465Trp) pathogenic missense AKT3 variant in both affected half-siblings. The variant was verified via Sanger sequencing and was not present in the DNA sample from the healthy mother, which was derived from peripheral blood, suggesting maternal germline mosaicism. In conclusion, this is the first report in which maternal germline mosaicism of a rare pathogenic AKT3 variant leads to autosomal dominantly inherited MPPH syndrome.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Dedos del Pie
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Polidactilia
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Patrón de Herencia
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Proteínas Proto-Oncogénicas c-akt
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Megalencefalia
/
Dedos
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Polimicrogiria
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Células Germinativas
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Hidrocefalia
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Mosaicismo
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
Exp Mol Pathol
Año:
2020
Tipo del documento:
Article