Gene discovery for Mendelian conditions via social networking: de novo variants in KDM1A cause developmental delay and distinctive facial features.

TitleGene discovery for Mendelian conditions via social networking: de novo variants in KDM1A cause developmental delay and distinctive facial features.
Publication TypeJournal Article
Year of Publication2016
AuthorsChong, JX, Yu, J-H, Lorentzen, P, Park, KM, Jamal, SM, Tabor, HK, Rauch, A, Saenz, MSifuentes, Boltshauser, E, Patterson, KE, Nickerson, DA, Bamshad, MJ
JournalGenet Med
Volume18
Issue8
Pagination788-95
Date Published2016 Aug
ISSN1530-0366
Abstract

PURPOSE: The pace of Mendelian gene discovery is slowed by the "n-of-1 problem"-the difficulty of establishing the causality of a putatively pathogenic variant in a single person or family. Identification of an unrelated person with an overlapping phenotype and suspected pathogenic variant in the same gene can overcome this barrier, but it is often impeded by lack of a convenient or widely available way to share data on candidate variants/genes among families, clinicians, and researchers.

METHODS: Social networking among families, clinicians, and researchers was used to identify three children with variants of unknown significance in KDM1A and similar phenotypes.

RESULTS: De novo variants in KDM1A underlie a new syndrome characterized by developmental delay and distinctive facial features.

CONCLUSION: Social networking is a potentially powerful strategy to discover genes for rare Mendelian conditions, particularly those with nonspecific phenotypic features. To facilitate the efforts of families to share phenotypic and genomic information with each other, clinicians, and researchers, we developed the Repository for Mendelian Genomics Family Portal (RMD-FP; http://uwcmg.org/#/family). Design and development of MyGene2 (http://www.mygene2.org), a Web-based tool that enables families, clinicians, and researchers to search for gene matches based on analysis of phenotype and exome data deposited into the RMD-FP, is under way.Genet Med 18 8, 788-795.

DOI10.1038/gim.2015.161
Alternate JournalGenet. Med.
PubMed ID26656649
PubMed Central IDPMC4902791
Grant ListU54 HG006493 / HG / NHGRI NIH HHS / United States
RC2 HG005608 / HG / NHGRI NIH HHS / United States
R00 HG004316 / HG / NHGRI NIH HHS / United States
R01 HD048895 / HD / NICHD NIH HHS / United States
UM1 HG006493 / HG / NHGRI NIH HHS / United States