DMRTA2 (DMRT5) is mutated in a novel cortical brain malformation

被引：23

作者：

Urquhart, J. E. ^{[1
,2
]}

Beaman, G. ^{[1
,2
]}

Byers, H. ^{[1
,2
]}

Roberts, N. A. ^{[3
]}

Chervinsky, E. ^{[4
]}

O'Sullivan, J. ^{[1
,2
]}

Pilz, D. ^{[5
]}

Fry, A. ^{[5
]}

Williams, S. G. ^{[1
,2
]}

Bhaskar, S. S. ^{[1
,2
]}

Khayat, M. ^{[4
]}

Simanovsky, N. ^{[6
]}

Shachar, I. B. ^{[7
]}

Shalev, S. A. ^{[4
,8
]}

Newman, W. G. ^{[1
,2
]}

机构：

[1] St Marys Hosp, MAHSC, Manchester Ctr Genom Med, Manchester M13 9WL, Lancs, England

[2] Univ Manchester, Inst Human Dev, Manchester Ctr Genom Med, Manchester, Lancs, England

[3] Univ Manchester, Inst Human Dev, Ctr Paediat & Child Hlth, Manchester, Lancs, England

[4] Emek Med Ctr, Genet Inst, Afula, Israel

[5] Univ Wales Hosp, Inst Med Genet, Cardiff CF4 4XN, S Glam, Wales

[6] Hadassah Hebrew Univ, Med Ctr, Dept Med Imaging, Jerusalem, Israel

[7] Ziv Hosp, Fac Med, Safed, Israel

[8] Rappaport Fac Med, Haifa, Israel

来源：

CLINICAL GENETICS | 2016年 / 89卷 / 06期

关键词：

agenesis corpus callosum; DMRT5; DMRTA2; lissencephaly; microcephaly; pachygyria; NEURONAL MIGRATION; CEREBRAL-CORTEX; NEUROGENESIS; ZEBRAFISH; MUTATIONS; GENES; SEX;

D O I：

10.1111/cge.12734

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Lissencephaly is a phenotypically and genetically heterogeneous group of cortical brain malformations due to abnormal neuronal migration. The identification of many causative genes has increased the understanding of normal brain development. A consanguineous family was ascertained with three siblings affected by a severe prenatal neurodevelopmental disorder characterised by fronto-parietal pachygyria, agenesis of the corpus callosum and progressive severe microcephaly. Autozygosity mapping and exome sequencing identified a homozygous novel single base pair deletion, c.1197delT in DMRTA2, predicted to result in a frameshift variant p.(Pro400Leufs*33). DMRTA2 encodes doublesex and mab-3-related transcription factor a2, a transcription factor key to the development of the dorsal telencephalon. Data from murine and zebrafish knockout models are consistent with the variant of DMTRA2 (DMRT5) as responsible for the cortical brain phenotype. Our study suggests that loss of function of DMRTA2 leads to a novel disorder of cortical development.

引用

页码：724 / 727

页数：4

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