Beta-propeller Protein-Associated Neurodegeneration, or BPAN, is a rare genetic condition caused by mutations in the WDR45 gene. It is characterized by seizures, complex epileptic encephalopathies, developmental delays, and neurodegenerative symptoms similar to those found in Parkinson’s disease and currently has no cure.

Sarah Chisholm launched the BPAN warriors organization 10 months after her own daughter’s diagnosis with BPAN, and came across Mastermind in her efforts to gather and organize all of the existing medical literature for BPAN. Her goal was simple – to find a cure for her daughter. Soon after, Genomenon reached out to see if we could assist in her cause, and we have now officially partnered with the BPAN Warriors.

See the December edition of The Journal of Precision Medicine for more information on Sarah’s story and what inspired our partnership.

This partnership has culminated in the development of a variant database for the WDR45 gene, which is now freely available to all researchers and pharmaceutical companies interested in exploring the data. The comprehensive dataset contains 107 unique variants*, all of which are interpreted according to the standards set by the American College of Medical Genetics (ACMG). These clinical criteria require information from three main sources: the medical literature (both clinical and functional studies), population databases, and computational predictions of effects on protein function. All of the evidence supporting these conclusions are organized for review in the Mastermind Reporter software.

Because of the rarity of BPAN as well as its high phenotypic variability and the resulting propensity for misdiagnosis, we included all variants within the WDR45 gene that were found in patients with BPAN or a disorder with similar clinical symptoms. Additionally, we took careful note of these symptoms, such that the phenotype of patients with WDR45 mutations can be characterized in further detail.

Overall, this dataset provides a comprehensive view of the genetic landscape of BPAN and related disorders harboring WDR45 mutations. It may be useful in the following ways:

• To aid diagnosis: Developing a more detailed understanding of the genetic causes of BPAN will assist in ensuring higher overall diagnostic rates and earlier individual diagnosis
• To aid therapeutic decisions: Investigating therapies that have been tested in BPAN patients and their success at managing symptoms in patients with specific clinical presentations can assist in deciding the best course of treatment for newly diagnosed patients
• To aid new therapy development: Functional studies involving variants in the WDR45 gene can provide a deeper understanding of the genetic mechanism for BPAN, which can aid in the development of targeted therapies

Below is the list of variants in the WDR45 gene:

Gene	Variant	Mastermind Link	Variant Type	Articles	Provisional ACMG Call
WDR45	p.R134X	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R134X	Nonsense	11	Pathogenic
WDR45	c.830+1G>A	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.830+1G>A	Splice Donor	8	Pathogenic
WDR45	p.R7X	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R7X	Nonsense	8	Pathogenic
WDR45	p.R234X	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R234X	Nonsense	7	Pathogenic
WDR45	p.Y336fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Y336fs	Frameshift	7	Pathogenic
WDR45	p.Q290X	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Q290X	Nonsense	6	Pathogenic
WDR45	p.W83X	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.W83X	Nonsense	6	Pathogenic
WDR45	c.235+1G>A	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.235+1G>A	Splice Donor	5	Pathogenic
WDR45	c.342-2A>C	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.342-2A>C	Splice Acceptor	5	Pathogenic
WDR45	p.E76fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.E76fs	Frameshift	5	Pathogenic
WDR45	p.G342fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.G342fs	Frameshift	5	Pathogenic
WDR45	p.I196fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.I196fs	Frameshift	5	Pathogenic
WDR45	p.L232fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L232fs	Frameshift	5	Pathogenic
WDR45	p.L98P	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L98P	Substitution	5	Pathogenic
WDR45	p.R7fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R7fs	Frameshift	5	Pathogenic
WDR45	c.131-1G>A	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.131-1G>A	Splice Acceptor	4	Pathogenic
WDR45	c.55+1G>C	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.55+1G>C	Splice Donor	4	Pathogenic
WDR45	c.56-1G>A	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.56-1G>A	Splice Acceptor	4	Pathogenic
WDR45	c.831-1G>C	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.831-1G>C	Splice Acceptor	4	Pathogenic
WDR45	p.D174fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.D174fs	Frameshift	4	Pathogenic
WDR45	p.G205D	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.G205D	Substitution	4	Pathogenic
WDR45	p.K121fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.K121fs	Frameshift	4	Pathogenic
WDR45	p.K135fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.K135fs	Frameshift	4	Pathogenic
WDR45	p.L148fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L148fs	Frameshift	4	Pathogenic
WDR45	p.L159fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L159fs	Frameshift	4	Pathogenic
WDR45	p.M1del	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.M1del	Deletion	4	Pathogenic
WDR45	p.N345fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.N345fs	Frameshift	4	Pathogenic
WDR45	p.Q213X	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Q213X	Nonsense	4	Pathogenic
WDR45	p.Q295fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Q295fs	Frameshift	4	Pathogenic
WDR45	p.V324fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.V324fs	Frameshift	4	Pathogenic
WDR45	p.Y352X	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Y352X	Nonsense	4	Pathogenic
WDR45	c.345-1G>A	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.345-1G>A	Splice Acceptor	3	Pathogenic
WDR45	c.439+1G>T	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.439+1G>T	Splice Donor	3	Pathogenic
WDR45	c.440-2A>G	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.440-2A>G	Splice Acceptor	3	Pathogenic
WDR45	c.830+2T>C	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.830+2T>C	Splice Donor	3	Pathogenic
WDR45	p.C149X	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.C149X	Nonsense	3	Pathogenic
WDR45	p.C22fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.C22fs	Frameshift	3	Pathogenic
WDR45	p.C344fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.C344fs	Frameshift	3	Pathogenic
WDR45	p.F221X	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.F221X	Nonsense	3	Pathogenic
WDR45	p.L201fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L201fs	Frameshift	3	Pathogenic
WDR45	p.L63fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L63fs	Frameshift	3	Pathogenic
WDR45	p.P163fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.P163fs	Frameshift	3	Pathogenic
WDR45	p.S108fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.S108fs	Frameshift	3	Pathogenic
WDR45	c.235+1G>T	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.235+1G>T	Splice Donor	2	Pathogenic
WDR45	p.C152fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.C152fs	Frameshift	2	Pathogenic
WDR45	p.F221fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.F221fs	Frameshift	2	Pathogenic
WDR45	p.L107fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L107fs	Frameshift	2	Pathogenic
WDR45	p.S184fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.S184fs	Frameshift	2	Pathogenic
WDR45	p.Y242X	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Y242X	Nonsense	2	Pathogenic
WDR45	c.344+1G>A	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.344+1G>A	Splice Donor	1	Pathogenic
WDR45	c.830+1G>C	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.830+1G>C	Splice Donor	1	Pathogenic
WDR45	p.A255fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.A255fs	Frameshift	1	Pathogenic
WDR45	p.A305fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.A305fs	Frameshift	1	Pathogenic
WDR45	p.A308fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.A308fs	Frameshift	1	Pathogenic
WDR45	p.C254X	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.C254X	Nonsense	1	Pathogenic
WDR45	p.D114X	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.D114X	Nonsense	1	Pathogenic
WDR45	p.D84fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.D84fs	Frameshift	1	Pathogenic
WDR45	p.E347fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.E347fs	Frameshift	1	Pathogenic
WDR45	p.S210fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.S210fs	Frameshift	1	Pathogenic
WDR45	p.Y291X	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Y291X	Nonsense	1	Pathogenic
WDR45	p.V54del	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.V54del	Deletion	6	Likely Pathogenic
WDR45	p.S251del	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.S251del	Deletion	5	Likely Pathogenic
WDR45	p.A209D	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.A209D	Substitution	4	Likely Pathogenic
WDR45	p.M1V	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.M1V	Substitution	4	Likely Pathogenic
WDR45	p.N61K	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.N61K	Substitution	4	Likely Pathogenic
WDR45	p.R13P	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R13P	Substitution	4	Likely Pathogenic
WDR45	p.E138del	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.E138del	Deletion	3	Likely Pathogenic
WDR45	p.F265fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.F265fs	Frameshift	2	Likely Pathogenic
WDR45	p.L266fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L266fs	Frameshift	2	Likely Pathogenic
WDR45	p.Q16X	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Q16X	Nonsense	2	Likely Pathogenic
WDR45	c.345-2A>C	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.345-2A>C	Splice Acceptor	1	Likely Pathogenic
WDR45	c.827+2T>G	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.827+2T>G	Splice Donor	1	Likely Pathogenic
WDR45	p.D113A	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.D113A	Substitution	1	Likely Pathogenic
WDR45	p.E155X	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.E155X	Nonsense	1	Likely Pathogenic
WDR45	p.F100S	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.F100S	Substitution	1	Likely Pathogenic
WDR45	p.G168E	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.G168E	Substitution	1	Likely Pathogenic
WDR45	p.K115X	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.K115X	Nonsense	1	Likely Pathogenic
WDR45	p.L160R	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L160R	Substitution	1	Likely Pathogenic
WDR45	p.N202K	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.N202K	Substitution	1	Likely Pathogenic
WDR45	p.Q171X	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Q171X	Nonsense	1	Likely Pathogenic
WDR45	p.R134P	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R134P	Substitution	1	Likely Pathogenic
WDR45	p.R219fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R219fs	Frameshift	1	Likely Pathogenic
WDR45	p.T260fs	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.T260fs	Frameshift	1	Likely Pathogenic
WDR45	p.V34M	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.V34M	Substitution	1	Likely Pathogenic
WDR45	p.D84G	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.D84G	Substitution	5	Variant of Uncertain Signifigance
WDR45	p.G147V	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.G147V	Substitution	3	Variant of Uncertain Signifigance
WDR45	p.R13X	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R13X	Nonsense	3	Variant of Uncertain Signifigance
WDR45	p.R7Q	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R7Q	Substitution	3	Variant of Uncertain Signifigance
WDR45	p.S210P	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.S210P	Substitution	3	Variant of Uncertain Signifigance
WDR45	c.236-18A>G	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.236-18A>G	Intronic	2	Variant of Uncertain Signifigance
WDR45	p.L278X	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L278X	Nonsense	2	Variant of Uncertain Signifigance
WDR45	p.Y336C	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Y336C	Substitution	2	Variant of Uncertain Signifigance
WDR45	c.344+4A>C	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.344+4A>C	Intronic	1	Variant of Uncertain Signifigance
WDR45	c.519+1_519+3del	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.519+1_519+3del	Splice Donor	1	Variant of Uncertain Signifigance
WDR45	p.A255S	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.A255S	Substitution	1	Variant of Uncertain Signifigance
WDR45	p.D17A	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.D17A	Substitution	1	Variant of Uncertain Signifigance
WDR45	p.L63W	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L63W	Substitution	1	Variant of Uncertain Signifigance
WDR45	p.N15A	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.N15A	Substitution	1	Variant of Uncertain Signifigance
WDR45	p.Q16A	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Q16A	Substitution	1	Variant of Uncertain Signifigance
WDR45	p.Q223del	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Q223del	Deletion	1	Variant of Uncertain Signifigance
WDR45	p.R112C	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R112C	Substitution	1	Variant of Uncertain Signifigance
WDR45	p.R112H	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R112H	Substitution	1	Variant of Uncertain Signifigance
WDR45	p.R233A	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R233A	Substitution	1	Variant of Uncertain Signifigance
WDR45	p.R274H	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R274H	Substitution	1	Variant of Uncertain Signifigance
WDR45	p.V230L	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.V230L	Substitution	1	Variant of Uncertain Signifigance
WDR45	p.Y291Y	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Y291Y	Synonymous	1	Variant of Uncertain Signifigance
WDR45	p.Q212del	https://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Q212del	Deletion	1	Variant of Uncertain Signifigance

We have been so inspired by Sarah’s story and the potential to make a difference in these parents’ quest that we have made the comprehensive genomic landscape of BPAN freely available to any pharmaceutical company or researcher interested in exploring the data. The availability of this data will not only help researchers better understand this rare disease, but will provide a solid foundation for pharmaceutical companies to begin the search for a cure with a resource that would otherwise take years to assemble.

* At the time the article in The Journal for Precision Medicine was written, there were 94 variants related to WDR45, but since the time of original publication, Mastermind has identified 13 new variants, taking the total to 107, all of which are in the current dataset.

To request access to the BPAN variant dataset, sign up below: