Mutation analysis of the DCX gene and genotype/phenotype correlation in subcortical band heterotopia

Naomichi Matsumoto; Richard J. Leventer; Julie A. Kuc; Stephanie K. Mewborn; Laura L. Dudlicek; Melissa B. Ramocki; Daniela T. Pilz; Patti L. Mills; Soma Das; M. Elizabeth Ross; David H. Ledbetter; William B. Dobyns

doi:10.1038/sj.ejhg.5200548

Mutation analysis of the DCX gene and genotype/phenotype correlation in subcortical band heterotopia

Naomichi Matsumoto, Richard J. Leventer, Julie A. Kuc, Stephanie K. Mewborn, Laura L. Dudlicek, Melissa B. Ramocki, Daniela T. Pilz, Patti L. Mills, Soma Das, M. Elizabeth Ross, David H. Ledbetter, William B. Dobyns

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132 Scopus citations

Abstract

Subcortical band heterotopia (SBH) comprises part of a spectrum of phenotypes associated with classical lissencephaly (LIS). LIS and SBH are caused by alterations in at least two genes: LIS1 (PAFAH1B1) at 17p13.3 and DCX (doublecortin) at Xq22.3-q23. DCX mutations predominantly cause LIS in hemizygous males and SBH in heterozygous females, and we have evaluated several families with LIS male and SBH female siblings. In this study, we performed detailed DCX mutation analysis and genotype-phenotype correlation in a large cohort with typical SBH. We screened 26 sporadic SBH females and 11 LIS/SBH families for DCX mutations by direct sequencing. We found 29 mutations in 22 sporadic patients and 11 pedigrees, including five deletions, four nonsense mutations, 19 missense mutations and one splice donor site mutation. The DCX mutation prevalence was 84.6% (22 of 26) in sporadic SBH patients and 100% (11 of 11) in SBH pedigrees. Maternal germline mosaicism was found in one family. Significant differences in genotype were found in relation to band thickness and familial vs sporadic status.

Original language	English (US)
Pages (from-to)	5-12
Number of pages	8
Journal	European Journal of Human Genetics
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/sj.ejhg.5200548
State	Published - 2001
Externally published	Yes

Bibliographical note

Funding Information:
We would like to thank all the families and clinicians whose co-operation made this study possible. This work was supported in part by grants from the National Institutes of Health to WBD, DHL and MER (P01-NS39404) and to MER and WBD (R01-NS35515), and by the Lissencephaly Network Inc. to The University of Chicago Department of Human Genetics.

Keywords

DCX
Mutations
Subcortical band heterotopia
X inactivation
XLIS

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Matsumoto, N., Leventer, R. J., Kuc, J. A., Mewborn, S. K., Dudlicek, L. L., Ramocki, M. B., Pilz, D. T., Mills, P. L., Das, S., Ross, M. E., Ledbetter, D. H., & Dobyns, W. B. (2001). Mutation analysis of the DCX gene and genotype/phenotype correlation in subcortical band heterotopia. European Journal of Human Genetics, 9(1), 5-12. https://doi.org/10.1038/sj.ejhg.5200548

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title = "Mutation analysis of the DCX gene and genotype/phenotype correlation in subcortical band heterotopia",

abstract = "Subcortical band heterotopia (SBH) comprises part of a spectrum of phenotypes associated with classical lissencephaly (LIS). LIS and SBH are caused by alterations in at least two genes: LIS1 (PAFAH1B1) at 17p13.3 and DCX (doublecortin) at Xq22.3-q23. DCX mutations predominantly cause LIS in hemizygous males and SBH in heterozygous females, and we have evaluated several families with LIS male and SBH female siblings. In this study, we performed detailed DCX mutation analysis and genotype-phenotype correlation in a large cohort with typical SBH. We screened 26 sporadic SBH females and 11 LIS/SBH families for DCX mutations by direct sequencing. We found 29 mutations in 22 sporadic patients and 11 pedigrees, including five deletions, four nonsense mutations, 19 missense mutations and one splice donor site mutation. The DCX mutation prevalence was 84.6% (22 of 26) in sporadic SBH patients and 100% (11 of 11) in SBH pedigrees. Maternal germline mosaicism was found in one family. Significant differences in genotype were found in relation to band thickness and familial vs sporadic status.",

keywords = "DCX, Mutations, Subcortical band heterotopia, X inactivation, XLIS",

author = "Naomichi Matsumoto and Leventer, {Richard J.} and Kuc, {Julie A.} and Mewborn, {Stephanie K.} and Dudlicek, {Laura L.} and Ramocki, {Melissa B.} and Pilz, {Daniela T.} and Mills, {Patti L.} and Soma Das and Ross, {M. Elizabeth} and Ledbetter, {David H.} and Dobyns, {William B.}",

note = "Funding Information: We would like to thank all the families and clinicians whose co-operation made this study possible. This work was supported in part by grants from the National Institutes of Health to WBD, DHL and MER (P01-NS39404) and to MER and WBD (R01-NS35515), and by the Lissencephaly Network Inc. to The University of Chicago Department of Human Genetics.",

year = "2001",

doi = "10.1038/sj.ejhg.5200548",

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AU - Mewborn, Stephanie K.

AU - Dudlicek, Laura L.

AU - Ramocki, Melissa B.

AU - Pilz, Daniela T.

AU - Mills, Patti L.

AU - Das, Soma

AU - Ross, M. Elizabeth

AU - Ledbetter, David H.

AU - Dobyns, William B.

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Mutation analysis of the DCX gene and genotype/phenotype correlation in subcortical band heterotopia

Abstract

Bibliographical note

Keywords

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