Mutation of the doublecortin gene in male patients with double cortex syndrome: Somatic mosaicism detected by hair root analysis

Abstract

The molecular basis of double cortex syndrome was investigated in 2 male patients. Magnetic resonance imaging of the patients' heads showed diffuse subcortical band heterotopia, as is seen in female patients. We found a heterozygous mutation for Asp50Lys or Arg39Stop in both patients. Microsatellite polymorphism analysis revealed that both patients had inherited a single X chromosome from their mothers. Restriction enzyme analysis using DNA extracted from the hair roots of each patient showed four different patterns in the combination of cells carrying wild and mutant alleles, which strongly suggest somatic mosaicism. We conclude that somatic mosaic mutations in the doublecortin gene in male patients can cause subcortical band heterotopia, and that molecular analysis using hair roots is a useful method for detecting somatic mosaicism.

Nonsyndromic mental retardation and cryptogenic epilepsy in women with Doublecortin gene mutations

“…We tested somatic mosaicism11, 15, 16 in patients 2‐II:2 and 3‐II:1, who had de novo mutations. Mosaicism was considered unlikely in carrier female subjects in Families 1 (1‐IV:5) and 4 (4‐II:12 and 4‐II:16).…”

Missense mutations resulting in type 1 lissencephaly

“…To date, more than 25 missense mutations in DCX were detected in patients [14,15,72,[119][120][121][122][123][124][125][126][127][128][129][130], interestingly, several of these sites were independently mutated several times. Our discussion will focus on those mutations CMLS, Cell.…”

Clinical implications of the detection of Y-chromosome mosaicism in Turner's syndrome: report of 3 cases

“…Because the patient was submitted to gonadectomy and presented more than one histopathologic hyperandrogenic abnormality, we believe that SRY expression could be related to this finding (hilus cell hyperplasia, stromal luteoma, and nodular hyperthecosis with immunopositivity for T). These lesions are associated with excessive androgen production (33), which explains the clinical manifestations of this patient. Patient C, who presented the same karyotype constitution as patient A and was only 22 years old at surgery, showed ovarian stroma, although ovarian follicles were absent.…”