Universität zu Köln

Lopez-Rivera, Javier A., Perez-Palma, Eduardo ORCID: 0000-0003-0546-5141, Symonds, Joseph ORCID: 0000-0002-2141-4216, Lindy, Amanda S., McKnight, Dianalee A., Leu, Costin, Zuberi, Sameer, Brunklaus, Andreas, Moller, Rikke S. and Lal, Dennis (2020). A catalogue of new incidence estimates of monogenic neurodevelopmental disorders caused by de novo variants. Brain, 143. S. 1099 - 1106. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2156

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Abstract

A large fraction of rare and severe neurodevelopmental disorders are caused by sporadic de novo variants. Epidemiological disease estimates are not available for the vast majority of these de novo monogenic neurodevelopmental disorders because of phenotypic heterogeneity and the absence of large-scale genomic screens. Yet, knowledge of disease incidence is important for clinicians and researchers to guide health policy planning. Here, we adjusted a statistical method based on genetic data to predict, for the first time, the incidences of 101 known de novo variant-associated neurodevelopmental disorders as well as 3106 putative monogenic disorders. Two corroboration analyses supported the validity of the calculated estimates. First, greater predicted gene-disorder incidences positively correlated with larger numbers of pathogenic variants collected from patient variant databases (Kendall's tau = 0.093, P-value = 6.9 x 10(-6)). Second, for six of seven (86%) de novo variant associated monogenic disorders for which epidemiological estimates were available (SCN1A, SLC2A1, SALL1, TBX5, KCNQ2, and CDKL5), the predicted incidence estimates matched the reported estimates. We conclude that in the absence of epidemiological data, our catalogue of 3207 incidence estimates for disorders caused by de novo variants can guide patient advocacy groups, clinicians, researchers, and policymakers in strategic decision-making.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lopez-Rivera, Javier A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Perez-Palma, Eduardo UNSPECIFIED orcid.org/0000-0003-0546-5141 UNSPECIFIED Symonds, Joseph UNSPECIFIED orcid.org/0000-0002-2141-4216 UNSPECIFIED Lindy, Amanda S. UNSPECIFIED UNSPECIFIED UNSPECIFIED McKnight, Dianalee A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Leu, Costin UNSPECIFIED UNSPECIFIED UNSPECIFIED Zuberi, Sameer UNSPECIFIED UNSPECIFIED UNSPECIFIED Brunklaus, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Moller, Rikke S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lal, Dennis UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-338090
DOI:	10.1093/brain/awaa051
Journal or Publication Title:	Brain
Volume:	143
Page Range:	S. 1099 - 1106
Date:	2020
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2156
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CONGENITAL HEART-DISEASE; DRAVET SYNDROME; MUTATIONS; PREVALENCE; EPILEPSY; DATABASE; GENES Multiple languages Clinical Neurology; Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33809