Center for Precision Medicine Models Publications

C-terminal frameshift variants in GPKOW are associated with a multisystemic X-linked disorder.

Mok JW, Mackay L, Blazo M, Mizerik E, Gecz J, Carroll R, Nizon M, Rondeau S, Joubert M, Cuinat S, Deb W, Sirias FV, Weisz-Hubshman M, Ketkar S, Polak U, Tran AA, Kearney D, Neil HA, Kanca O, Wangler MF, Bellen HJ, Lee BH, Yamamoto S, Machol K. Genet Med. 2025 Apr 9:101429. doi: 10.1016/j.gim.2025.101429. PMID: 40221893

Uncovering Phenotypic Expansion in AXIN2-Related Disorders through Precision Animal Modeling.

Aceves-Ewing NM, Lanza DG, Marcogliese PC, Lu D, Hsu CW, Gonzalez M, Christiansen AE, Rasmussen TL, Ho AJ, Gaspero A, Seavitt J, Dickinson ME, Yuan B, Shayota BJ, Pachter S, Hu X, Day-Salvatore DL, Mackay L, Kanca O, Wangler MF, Potocki L, Rosenfeld JA, Lewis RA, Chao HT, Lee B, Lee S; Undiagnosed Diseases Network; Baylor College of Medicine Center for Precision Medicine Models; Yamamoto S, Bellen HJ, Burrage LC, Heaney JD.  medRxiv [Preprint]. 2024 Dec 8:2024.12.05.24318524. doi: 10.1101/2024.12.05.24318524. PMID: 39677486; PMCID: PMC11643287.

De novo and inherited variants in DDX39B cause a novel neurodevelopmental syndrome.

Booth KTA, Jangam SV, Chui MMC, Treat K, Graziani L, Soldano A, Ruan Y, Wan-Hei Hui J, White K, Christensen CK, Lynnes T, Yamamoto S, Kanca O, Tsang MHY, Lynch SA, Mullegama SV, Batista J, Iancu D, Joss SK, Wong SYY, Mak CCY, Kwong AKY, Bellen HJ, Conboy E, Sanges R, Leung AY, Wangler MF, Chung BHY, Vetrini F.  Brain. 2025 Feb 7:awaf035. doi: 10.1093/brain/awaf035. Epub ahead of print. PMID: 39918047.

An oocyte-specific Cas9-expressing mouse for germline CRISPR/Cas9-mediated genome editing. 

Lanza DG, Mao J, Lorenzo I, Liao L, Seavitt JR, Ljungberg MC, Simpson EM, DeMayo FJ, Heaney JD. Genesis. 2024 Apr;62(2):e23589. doi: 10.1002/dvg.23589. PMID: 38523431; PMCID: PMC10987075.

Alzheimer's disease risk gene CD2AP is a dose-sensitive determinant of synaptic structure and plasticity. 

Pavešković M, De-Paula RB, Ojelade SA, Tantry EK, Kochukov MY, Bao S, Veeraragavan S, Garza AR, Srivastava S, Song SY, Fujita M, Duong DM, Bennett DA, De Jager PL, Seyfried NT, Dickinson ME, Heaney JD, Arenkiel BR, Shulman JM. Hum Mol Genet. 2024 Oct 7; 33(20): 1815-1832. doi: 10.1093/hmg/ddae115. PMID: 39146503; PMCID: PMC11458016.

Impact of essential genes on the success of genome editing experiments generating 3313 new genetically engineered mouse lines. 

Elrick H, Peterson KA, Willis BJ, Lanza DG, Acar EF, Ryder EJ, Teboul L, Kasparek P, Birling MC, Adams DJ, Bradley A, Braun RE, Brown SD, Caulder A, Codner GF, DeMayo FJ, Dickinson ME, Doe B, Duddy G, Gertsenstein M, Goodwin LO, Hérault Y, Lintott LG, Lloyd KCK, Lorenzo I, Mackenzie M, Mallon AM, McKerlie C, Parkinson H, Ramirez-Solis R, Seavitt JR, Sedlacek R, Skarnes WC, Smedley D, Wells S, White JK, Wood JA; International Mouse Phenotyping Consortium; Murray SA, Heaney JD, Nutter LMJ. Sci Rep. 2024 Sep 30; 14(1): 22626. doi: 10.1038/s41598-024-72418-8. PMID: 39349521; PMCID: PMC11443006.

Dominant missense variants in SREBF2 are associated with complex dermatological, neurological, and skeletal abnormalities.

Moulton MJ, Atala K, Zheng Y, Dutta D, Grange DK, Lin WW, Wegner DJ, Wambach JA, Duker AL, Bober MB, Kratz L, Wise CA, Oxendine I, Khanshour A; Undiagnosed Diseases Network; Wangler MF, Yamamoto S, Cole FS, Rios J, Bellen HJ.  Genet Med. 2024 Sep; 26(9): 101174. doi: 10.1016/j.gim.2024.101174. Epub 2024 Jun 3. PMID: 38847193.

The IFITM5 mutation in osteogenesis imperfecta type V is associated with an ERK/SOX9-dependent osteoprogenitor differentiation defect.

Marom R, Song IW, Busse EC, Washington ME, Berrier AS, Rossi VC, Ortinau L, Jeong Y, Jiang MM, Dawson BC, Adeyeye M, Leynes C, Lietman CD, Stroup BM, Batkovskyte D, Jain M, Chen Y, Cela R, Castellon A, Tran AA, Lorenzo I, Meyers DN, Huang S, Turner A, Shenava V, Wallace M, Orwoll E, Park D, Ambrose CG, Nagamani SC, Heaney JD, Lee BH.  J Clin Invest. 2024 Jun 17; 134(15): e170369. doi: 10.1172/JCI170369. PMID: 38885336; PMCID: PMC11290974.

AI-MARRVEL - A Knowledge-Driven AI System for Diagnosing Mendelian Disorders.

Mao D, Liu C, Wang L, Ai-Ouran R, Deisseroth C, Pasupuleti S, Kim SY, Li L, Rosenfeld JA, Meng L, Burrage LC, Wangler MF, Yamamoto S; Undiagnosed Diseases Network; Santana M, Perez V, Shukla P, Eng CM, Lee B, Yuan B, Xia F, Bellen HJ, Liu P, Liu Z. NEJM AI. 2024 May; 1(5): 10.1056/aioa2300009. doi: 10.1056/aioa2300009. Epub 2024 Apr 25. PMID: 38962029; PMCID: PMC11221788.

Gain-of-function and loss-of-function variants in GRIA3 lead to distinct neurodevelopmental phenotypes. 

Rinaldi B, Bayat A, Zachariassen LG, Sun JH, Ge YH, Zhao D, Bonde K, Madsen LH, Awad IAA, Bagiran D, Sbeih A, Shah SM, El-Sayed S, Lyngby SM, Pedersen MG, Stenum-Berg C, Walker LC, Krey I, Delahaye-Duriez A, Emrick LT, Sully K, Murali CN, Burrage LC, Plaud Gonzalez JA, Parnes M, Friedman J, Isidor B, Lefranc J, Redon S, Heron D, Mignot C, Keren B, Fradin M, Dubourg C, Mercier S, Besnard T, Cogne B, Deb W, Rivier C, Milani D, Bedeschi MF, Di Napoli C, Grilli F, Marchisio P, Koudijs S, Veenma D, Argilli E, Lynch SA, Au PYB, Ayala Valenzuela FE, Brown C, Masser-Frye D, Jones M, Patron Romero L, Li WL, Thorpe E, Hecher L, Johannsen J, Denecke J, McNiven V, Szuto A, Wakeling E, Cruz V, Sency V, Wang H, Piard J, Kortüm F, Herget T, Bierhals T, Condell A, Ben-Zeev B, Kaur S, Christodoulou J, Piton A, Zweier C, Kraus C, Micalizzi A, Trivisano M, Specchio N, Lesca G, Møller RS, Tümer Z, Musgaard M, Gerard B, Lemke JR, Shi YS, Kristensen AS. Brain. 2024 May 3; 147(5): 1837-1855. doi: 10.1093/brain/awad403. PMID: 38038360; PMCID: PMC11068105.

De novo variants in FRYL are associated with developmental delay, intellectual disability, and dysmorphic features.

Pan X, Tao AM, Lu S, Ma M, Hannan SB, Slaugh R, Drewes Williams S, O'Grady L, Kanca O, Person R, Carter MT, Platzer K, Schnabel F, Abou Jamra R, Roberts AE, Newburger JW, Revah-Politi A, Granadillo JL, Stegmann APA, Sinnema M, Accogli A, Salpietro V, Capra V, Ghaloul-Gonzalez L, Brueckner M, Simon MEH, Sweetser DA, Glinton KE, Kirk SE; Baylor College of Medicine Center for Precision Medicine Models; Wangler MF, Yamamoto S, Chung WK, Bellen HJ.  Am J Hum Genet. 2024 Apr 4; 111(4): 742-760. doi: 10.1016/j.ajhg.2024.02.007. Epub 2024 Mar 12. PMID: 38479391; PMCID: PMC11023917.

Heterozygous MAP3K20 variants cause ectodermal dysplasia, craniosynostosis, sensorineural hearing loss, and limb anomalies. 

Brooks D, Burke E, Lee S, Eble TN, O'Leary M, Osei-Owusu I, Rehm HL, Dhar SU, Emrick L, Bick D, Nehrebecky M, Macnamara E, Casas-Alba D, Armstrong J, Prat C, Martínez-Monseny AF, Palau F, Liu P, Adams D; Undiagnosed Diseases Network; Lalani S, Rosenfeld JA, Burrage LC. Hum Genet. 2024 Mar; 143(3): 279-291. doi: 10.1007/s00439-024-02657-2. Epub 2024 Mar 7. PMID: 38451290; PMCID: PMC11191325.

Integrating non-mammalian model organisms in the diagnosis of rare genetic diseases in humans.

Yamamoto S, Kanca O, Wangler MF, Bellen HJ.  Nat Rev Genet. 2024 Jan; 25(1): 46-60. doi: 10.1038/s41576-023-00633-6. Epub 2023 Jul 25. PMID: 37491400.

Allelic strengths of encephalopathy-associated UBA5 variants correlate between in vivo and in vitro assays. 

Pan X, Alvarez AN, Ma M, Lu S, Crawford MW, Briere LC, Kanca O, Yamamoto S, Sweetser DA, Wilson JL, Napier RJ, Pruneda JN, Bellen HJ. Elife. 2023 Dec 11; 12: RP89891. doi: 10.7554/eLife.89891. PMID: 38079206; PMCID: PMC10712953.

Rare de novo gain-of-function missense variants in DOT1L are associated with developmental delay and congenital anomalies.

Nil Z, Deshwar AR, Huang Y, Barish S, Zhang X, Choufani S, Le Quesne Stabej P, Hayes I, Yap P, Haldeman-Englert C, Wilson C, Prescott T, Tveten K, Vøllo A, Haynes D, Wheeler PG, Zon J, Cytrynbaum C, Jobling R, Blyth M, Banka S, Afenjar A, Mignot C, Robin-Renaldo F, Keren B, Kanca O, Mao X, Wegner DJ, Sisco K, Shinawi M; Undiagnosed Disease Network; Wangler MF, Weksberg R, Yamamoto S, Costain G, Bellen HJ.  Am J Hum Genet. 2023 Nov 2; 110(11): 1919-1937. doi: 10.1016/j.ajhg.2023.09.009. Epub 2023 Oct 11. PMID: 37827158; PMCID: PMC10645550.

RNA Sequencing as a Diagnostic Tool.

Ketkar S, Burrage LC, Lee B. JAMA. 2023 Jan 3; 329(1): 85-86. doi: 10.1001/jama.2022.22843. PMID: 36525251.

Promoting validation and cross-phylogenetic integration in model organism research.

Cheng KC, Burdine RD, Dickinson ME, Ekker SC, Lin AY, Lloyd KCK, Lutz CM, MacRae CA, Morrison JH, O'Connor DH, Postlethwait JH, Rogers CD, Sanchez S, Simpson JH, Talbot WS, Wallace DC, Weimer JM, Bellen HJ. Dis Model Mech. 2022 Sep 1; 15(9): dmm049600. doi: 10.1242/dmm.049600. Epub 2022 Sep 20. PMID: 36125045; PMCID: PMC9531892.

COPB2 loss of function causes a coatopathy with osteoporosis and developmental delay. 

Marom R, Burrage LC, Venditti R, Clément A, Blanco-Sánchez B, Jain M, Scott DA, Rosenfeld JA, Sutton VR, Shinawi M, Mirzaa G, DeVile C, Roberts R, Calder AD, Allgrove J, Grafe I, Lanza DG, Li X, Joeng KS, Lee YC, Song IW, Sliepka JM, Batkovskyte D, Washington M, Dawson BC, Jin Z, Jiang MM, Chen S, Chen Y, Tran AA, Emrick LT, Murdock DR, Hanchard NA, Zapata GE, Mehta NR, Weis MA, Scott AA, Tremp BA, Phillips JB, Wegner J, Taylor-Miller T, Gibbs RA, Muzny DM, Jhangiani SN, Hicks J, Stottmann RW, Dickinson ME, Seavitt JR, Heaney JD, Eyre DR; Undiagnosed Diseases Network; Westerfield M, De Matteis MA, Lee B. Am J Hum Genet. 2021 Sep 2; 108(9): 1710-1724. doi: 10.1016/j.ajhg.2021.08.002. Epub 2021 Aug 26. PMID: 34450031; PMCID: PMC8456174.

Drosophila as a Model for Infectious Diseases.

Harnish JM, Link N, Yamamoto S. Int J Mol Sci. 2021 Mar 8; 22(5): 2724. doi: 10.3390/ijms22052724. PMID: 33800390; PMCID: PMC7962867.

A global Slc7a7 knockout mouse model demonstrates characteristic phenotypes of human lysinuric protein intolerance.

Stroup BM, Marom R, Li X, Hsu CW, Chang CY, Truong LD, Dawson B, Grafe I, Chen Y, Jiang MM, Lanza D, Green JR, Sun Q, Barrish JP, Ani S, Christiansen AE, Seavitt JR, Dickinson ME, Kheradmand F, Heaney JD, Lee B, Burrage LC. Hum Mol Genet. 2020 Aug 3; 29(13): 2171-2184. doi: 10.1093/hmg/ddaa107. PMID: 32504080; PMCID: PMC7399531.

De Novo Variants in CDK19 Are Associated with a Syndrome Involving Intellectual Disability and Epileptic Encephalopathy.

Chung HL, Mao X, Wang H, Park YJ, Marcogliese PC, Rosenfeld JA, Burrage LC, Liu P, Murdock DR, Yamamoto S, Wangler MF; Undiagnosed Diseases Network, Chao HT, Long H, Feng L, Bacino CA, Bellen HJ, Xiao B. Am J Hum Genet. 2020 May 7; 106(5): 717-725. doi: 10.1016/j.ajhg.2020.04.001. Epub 2020 Apr 23. PMID: 32330417; PMCID: PMC7212481.

Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms.

Chung HL, Wangler MF, Marcogliese PC, Jo J, Ravenscroft TA, Zuo Z, Duraine L, Sadeghzadeh S, Li-Kroeger D, Schmidt RE, Pestronk A, Rosenfeld JA, Burrage L, Herndon MJ, Chen S; Members of Undiagnosed Diseases Network, Shillington A, Vawter-Lee M, Hopkin R, Rodriguez-Smith J, Henrickson M, Lee B, Moser AB, Jones RO, Watkins P, Yoo T, Mar S, Choi M, Bucelli RC, Yamamoto S, Lee HK, Prada CE, Chae JH, Vogel TP, Bellen HJ. Neuron. 2020 May 20; 106(4): 589-606.e6. doi: 10.1016/j.neuron.2020.02.021. Epub 2020 Mar 12. PMID: 32169171; PMCID: PMC7289150.

BICRA, a SWI/SNF Complex Member, Is Associated with BAF-Disorder Related Phenotypes in Humans and Model Organisms.

Barish S, Barakat TS, Michel BC, Mashtalir N, Phillips JB, Valencia AM, Ugur B, Wegner J, Scott TM, Bostwick B; Undiagnosed Diseases Network, Murdock DR, Dai H, Perenthaler E, Nikoncuk A, van Slegtenhorst M, Brooks AS, Keren B, Nava C, Mignot C, Douglas J, Rodan L, Nowak C, Ellard S, Stals K, Lynch SA, Faoucher M, Lesca G, Edery P, Engleman KL, Zhou D, Thiffault I, Herriges J, Gass J, Louie RJ, Stolerman E, Washington C, Vetrini F, Otsubo A, Pratt VM, Conboy E, Treat K, Shannon N, Camacho J, Wakeling E, Yuan B, Chen CA, Rosenfeld JA, Westerfield M, Wangler M, Yamamoto S, Kadoch C, Scott DA, Bellen HJ. Am J Hum Genet. 2020 Dec 3; 107(6): 1096-1112. doi: 10.1016/j.ajhg.2020.11.003. Epub 2020 Nov 23. PMID: 33232675; PMCID: PMC7820627.

De novo mutations in TOMM70, a receptor of the mitochondrial import translocase, cause neurological impairment.

Dutta D, Briere LC, Kanca O, Marcogliese PC, Walker MA, High FA, Vanderver A, Krier J, Carmichael N, Callahan C, Taft RJ, Simons C, Helman G, Network UD, Wangler MF, Yamamoto S, Sweetser DA, Bellen HJ. Hum Mol Genet. 2020 Jun 3; 29(9): 1568-1579. doi: 10.1093/hmg/ddaa081. PMID: 32356556; PMCID: PMC7268787.

Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders.

Guo H, Bettella E, Marcogliese PC, Zhao R, Andrews JC, Nowakowski TJ, Gillentine MA, Hoekzema K, Wang T, Wu H, Jangam S, Liu C, Ni H, Willemsen MH, van Bon BW, Rinne T, Stevens SJC, Kleefstra T, Brunner HG, Yntema HG, Long M, Zhao W, Hu Z, Colson C, Richard N, Schwartz CE, Romano C, Castiglia L, Bottitta M, Dhar SU, Erwin DJ, Emrick L, Keren B, Afenjar A, Zhu B, Bai B, Stankiewicz P, Herman K; University of Washington Center for Mendelian Genomics, Mercimek-Andrews S, Juusola J, Wilfert AB, Abou Jamra R, Büttner B, Mefford HC, Muir AM, Scheffer IE, Regan BM, Malone S, Gecz J, Cobben J, Weiss MM, Waisfisz Q, Bijlsma EK, Hoffer MJV, Ruivenkamp CAL, Sartori S, Xia F, Rosenfeld JA, Bernier RA, Wangler MF, Yamamoto S, Xia K, Stegmann APA, Bellen HJ, Murgia A, Eichler EE. Nat Commun. 2019 Oct 15; 10(1): 4679. doi:10.1038/s41467-019-12435-8. PMID: 31616000; PMCID: PMC6794285.

Bi-allelic Variants in TONSL Cause SPONASTRIME Dysplasia and a Spectrum of Skeletal Dysplasia Phenotypes.

Burrage LC, Reynolds JJ, Baratang NV, Phillips JB, Wegner J, McFarquhar A, Higgs MR, Christiansen AE, Lanza DG, Seavitt JR, Jain M, Li X, Parry DA, Raman V, Chitayat D, Chinn IK, Bertuch AA, Karaviti L, Schlesinger AE, Earl D, Bamshad M, Savarirayan R, Doddapaneni H, Muzny D, Jhangiani SN, Eng CM, Gibbs RA, Bi W, Emrick L, Rosenfeld JA, Postlethwait J, Westerfield M, Dickinson ME, Beaudet AL, Ranza E, Huber C, Cormier-Daire V, Shen W, Mao R, Heaney JD, Orange JS; University of Washington Center for Mendelian Genomics; Undiagnosed Diseases Network, Bertola D, Yamamoto GL, Baratela WAR, Butler MG, Ali A, Adeli M, Cohn DH, Krakow D, Jackson AP, Lees M, Offiah AC, Carlston CM, Carey JC, Stewart GS, Bacino CA, Campeau PM, Lee B. Am J Hum Genet. 2019 Mar 7; 104(3): 422-438. doi: 10.1016/j.ajhg.2019.01.007. Epub 2019 Feb 14. PMID: 30773277; PMCID: PMC6408318.

De Novo Variants in WDR37 Are Associated with Epilepsy, Colobomas, Dysmorphism, Developmental Delay, Intellectual Disability, and Cerebellar Hypoplasia.

Kanca O, Andrews JC, Lee PT, Patel C, Braddock SR, Slavotinek AM, Cohen JS, Gubbels CS, Aldinger KA, Williams J, Indaram M, Fatemi A, Yu TW, Agrawal PB, Vezina G, Simons C, Crawford J, Lau CC; Undiagnosed Diseases Network, Chung WK, Markello TC, Dobyns WB, Adams DR, Gahl WA, Wangler MF, Yamamoto S, Bellen HJ, Malicdan MCV. Am J Hum Genet. 2019 Sep 5; 105(3): 672-674. doi: 10.1016/j.ajhg.2019.07.017. Erratum for: Am J Hum Genet. 2019 Aug 1; 105(2): 413-424. PMID: 31491411; PMCID: PMC6732524.

Clinically severe CACNA1A alleles affect synaptic function and neurodegeneration differentially.

Luo X, Rosenfeld JA, Yamamoto S, Harel T, Zuo Z, Hall M, Wierenga KJ, Pastore MT, Bartholomew D, Delgado MR, Rotenberg J, Lewis RA, Emrick L, Bacino CA, Eldomery MK, Coban Akdemir Z, Xia F, Yang Y, Lalani SR, Lotze T, Lupski JR, Lee B, Bellen HJ, Wangler MF; Members of the UDN. PLoS Genet. 2017 Jul 24; 13(7): e1006905. doi: 10.1371/journal.pgen.1006905. PMID: 28742085; PMCID: PMC5557584.

Biallelic Variants in OTUD6B Cause an Intellectual Disability Syndrome Associated with Seizures and Dysmorphic Features.

Santiago-Sim T, Burrage LC, Ebstein F, Tokita MJ, Miller M, Bi W, Braxton AA, Rosenfeld JA, Shahrour M, Lehmann A, Cogné B, Küry S, Besnard T, Isidor B, Bézieau S, Hazart I, Nagakura H, Immken LL, Littlejohn RO, Roeder E; EuroEPINOMICS RES Consortium Autosomal Recessive working group, S. Hande Caglayan, Kara B, Hardies K, Weckhuysen S, May P, Lemke JR, Elpeleg O, Abu- Libdeh B, James KN, Silhavy JL, Issa MY, Zaki MS, Gleeson JG, Seavitt JR, Dickinson ME, Ljungberg MC, Wells S, Johnson SJ, Teboul L, Eng CM, Yang Y, Kloetzel PM, Heaney JD, Walkiewicz MA. Am J Hum Genet. 2017 Apr 6; 100(4): 676-688. doi: 10.1016/j.ajhg.2017.03.001. Epub 2017 Mar 23. PMID: 28343629; PMCID: PMC5384096.