Details

Autor(en) / Beteiligte

• Urquhart, J.E.
• Beaman, G.
• Byers, H.
• Roberts, N.A.
• Chervinsky, E.
• O'Sullivan, J.
• Pilz, D.
• Fry, A.
• Williams, S.G.
• Bhaskar, S.S.
• Khayat, M.
• Simanovsky, N.
• Shachar, I.B.
• Shalev, S.A.
• Newman, W.G.

Titel

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

Ist Teil von

• Clinical genetics, 2016-06, Vol.89 (6), p.724-727

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2016

Quelle

Wiley Online Journals

Beschreibungen/Notizen

• 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.