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Characterization of mutations in the gene doublecortin in patients with double cortex syndrome
Author(s) -
Gleeson Joseph G.,
Minnerath Sharon R.,
Fox Jeremy W.,
Allen Kristina M.,
Luo Robert F.,
Hong Susan E.,
Berg Michael J.,
Kuzniecky Ruben,
Reitnauer Pamela J.,
Borgatti Renato,
Puche Mira Alberto,
Guerrini Renzo,
Holmes Gregory L.,
Rooney Cynthia M.,
Berkovic Samuel,
Scheffer Ingrid,
Cooper Edward C.,
Ricci Stefano,
Cusmai Raffaella,
Crawford Thomas O.,
Leroy Robert,
Andermann Eva,
Wheless James W.,
Dobyns William B.,
Ross M. Elizabeth,
Walsh Christopher A.
Publication year - 1999
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(199902)45:2<146::aid-ana3>3.0.co;2-n
Subject(s) - doublecortin , genetics , biology , missense mutation , open reading frame , mutation , lissencephaly , frameshift mutation , microbiology and biotechnology , gene , peptide sequence , endocrinology , hippocampal formation , dentate gyrus
Mutations in the X‐linked gene doublecortin , which encodes a protein with no clear structural homologues, are found in pedigrees in which affected females show “double cortex” syndrome (DC; also known as subcortical band heterotopia or laminar heterotopia) and affected males show X‐linked lissencephaly. Mutations in doublecortin also cause sporadic DC in females. To determine the incidence of doublecortin mutations in DC, we investigated a cohort of eight pedigrees and 47 sporadic patients with DC for mutations in the doublecortin open reading frame as assessed by single‐stranded conformational polymorphism analysis. Mutations were identified in each of the eight DC pedigrees (100%), and in 18 of the 47 sporadic DC patients (38%). Identified mutations were of two types, protein truncation mutations and single amino acid substitution mutations. However, pedigrees with DC displayed almost exclusively single amino acid substitution mutations, suggesting that patients with these mutations may have less of a reproductive disadvantage versus those patients with protein truncation mutations. Single amino acid substitution mutations were tightly clustered in two regions of the open reading frame, suggesting that these two regions are critical for the function of the Doublecortin protein. Ann Neurol 1999;45:146–153