A new allelic variant of periventricular nodular heterotopia type 7 in a patient with adrenogenital syndrome due to a 21-hydroxylase deficiency

Abstract

We report 2-year-old girl with two monogenic diseases - adrenogenital syndrome with autosomal recessive inheritance mode and periventricular nodular heterotopia type 7 with autosomal dominant, diagnosed by two different molecular genetic methods. The presence of adreno-genital syndrome diagnosed in the first days of life based on typical clinical manifestations and the homozygous mutation was detected p.R356Wby direct DNA testing CYP21А2 gene. The presence of the second monogenic disease was proposed base on the observation the severe delay of psychomotor and speech development and abnormalities of the brain structure detected by MRI. Clinical exome sequencing identified previously not described single nucleotide substitution c.2015С>T (p.W672I) in NEDD4L gene. Pathogenic variants in HECT domain of this protein lead to periventricular nodular heterotopia type 7 (OMIM:617021). Analysis of segregation this variant in the family by direct sequencing of Sanger showed its origin de novo.