Functional correlation of genome-wide DNA methylation profiles in genetic neurodevelopmental disorders

Michael A. Levy; Raissa Relator; Haley McConkey; Erinija Pranckeviciene; Jennifer Kerkhof; Mouna Barat-Houari; Sara Bargiacchi; Elisa Biamino; María Palomares Bralo; Gerarda Cappuccio; Andrea Ciolfi; Angus Clarke; Barbara R. DuPont; Mariet W. Elting; Laurence Faivre; Timothy Fee; Marco Ferilli; Robin S. Fletcher; Florian Cherick; Aidin Foroutan; Michael J. Friez; Cristina Gervasini; Sadegheh Haghshenas; Benjamin A. Hilton; Zandra Jenkins; Simranpreet Kaur; Suzanne Lewis; Raymond J. Louie; Silvia Maitz; Donatella Milani; Angela T. Morgan; Renske Oegema; Elsebet Østergaard; Nathalie R. Pallares; Maria Piccione; Astrid S. Plomp; Cathryn Poulton; Jack Reilly; Rocio Rius; Stephen Robertson; Kathleen Rooney; Justine Rousseau; Gijs W.E. Santen; Fernando Santos-Simarro; Josephine Schijns; Gabriella M. Squeo; Miya St John; Christel Thauvin-Robinet; Giovanna Traficante; Pleuntje J. van der Sluijs; Samantha A. Vergano; Niels Vos; Kellie K. Walden; Dimitar Azmanov; Tugce B. Balci; Siddharth Banka; Jozef Gecz; Peter Henneman; Jennifer A. Lee; Marcel M.A.M. Mannens; Tony Roscioli; Victoria Siu; David J. Amor; Gareth Baynam; Eric G. Bend; Kym Boycott; Nicola Brunetti-Pierri; Philippe M. Campeau; Dominique Campion; John Christodoulou; David Dyment; Natacha Esber; Jill A. Fahrner; Mark D. Fleming; David Genevieve; Delphine Heron; Thomas Husson; Kristin D. Kernohan; Alisdair McNeill; Leonie A. Menke; Giuseppe Merla; Paolo Prontera; Cheryl Rockman-Greenberg; Charles Schwartz; Steven A. Skinner; Roger E. Stevenson; Marie Vincent; Antonio Vitobello; Marco Tartaglia; Marielle Alders; Matthew L. Tedder; Bekim Sadikovic

doi:10.1002/humu.24446

Functional correlation of genome-wide DNA methylation profiles in genetic neurodevelopmental disorders

Michael A. Levy, Raissa Relator, Haley McConkey, Erinija Pranckeviciene, Jennifer Kerkhof, Mouna Barat-Houari, Sara Bargiacchi, Elisa Biamino, María Palomares Bralo, Gerarda Cappuccio, Andrea Ciolfi, Angus Clarke, Barbara R. DuPont, Mariet W. Elting, Laurence Faivre, Timothy Fee, Marco Ferilli, Robin S. Fletcher, Florian Cherick, Aidin ForoutanMichael J. Friez, Cristina Gervasini, Sadegheh Haghshenas, Benjamin A. Hilton, Zandra Jenkins, Simranpreet Kaur, Suzanne Lewis, Raymond J. Louie, Silvia Maitz, Donatella Milani, Angela T. Morgan, Renske Oegema, Elsebet Østergaard, Nathalie R. Pallares, Maria Piccione, Astrid S. Plomp, Cathryn Poulton, Jack Reilly, Rocio Rius, Stephen Robertson, Kathleen Rooney, Justine Rousseau, Gijs W.E. Santen, Fernando Santos-Simarro, Josephine Schijns, Gabriella M. Squeo, Miya St John, Christel Thauvin-Robinet, Giovanna Traficante, Pleuntje J. van der Sluijs, Samantha A. Vergano, Niels Vos, Kellie K. Walden, Dimitar Azmanov, Tugce B. Balci, Siddharth Banka, Jozef Gecz, Peter Henneman, Jennifer A. Lee, Marcel M.A.M. Mannens, Tony Roscioli, Victoria Siu, David J. Amor, Gareth Baynam, Eric G. Bend, Kym Boycott, Nicola Brunetti-Pierri, Philippe M. Campeau, Dominique Campion, John Christodoulou, David Dyment, Natacha Esber, Jill A. Fahrner, Mark D. Fleming, David Genevieve, Delphine Heron, Thomas Husson, Kristin D. Kernohan, Alisdair McNeill, Leonie A. Menke, Giuseppe Merla, Paolo Prontera, Cheryl Rockman-Greenberg, Charles Schwartz, Steven A. Skinner, Roger E. Stevenson, Marie Vincent, Antonio Vitobello, Marco Tartaglia, Marielle Alders, Matthew L. Tedder, Bekim Sadikovic^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

40 Citations (Scopus)

8 Downloads (Pure)

Abstract

An expanding range of genetic syndromes are characterized by genome-wide disruptions in DNA methylation profiles referred to as episignatures. Episignatures are distinct, highly sensitive, and specific biomarkers that have recently been applied in clinical diagnosis of genetic syndromes. Episignatures are contained within the broader disorder-specific genome-wide DNA methylation changes, which can share significant overlap among different conditions. In this study, we performed functional genomic assessment and comparison of disorder-specific and overlapping genome-wide DNA methylation changes related to 65 genetic syndromes with previously described episignatures. We demonstrate evidence of disorder-specific and recurring genome-wide differentially methylated probes (DMPs) and regions (DMRs). The overall distribution of DMPs and DMRs across the majority of the neurodevelopmental genetic syndromes analyzed showed substantial enrichment in gene promoters and CpG islands, and under-representation of the more variable intergenic regions. Analysis showed significant enrichment of the DMPs and DMRs in gene pathways and processes related to neurodevelopment, including neurogenesis, synaptic signaling and synaptic transmission. This study expands beyond the diagnostic utility of DNA methylation episignatures by demonstrating correlation between the function of the mutated genes and the consequent genomic DNA methylation profiles as a key functional element in the molecular etiology of genetic neurodevelopmental disorders.

Original language	English
Journal	Human Mutation
Volume	43
Issue number	11
Pages (from-to)	1609-1628
ISSN	1059-7794
DOIs	https://doi.org/10.1002/humu.24446
Publication status	Published - 2022

Bibliographical note

Publisher Copyright:
© 2022 Wiley Periodicals LLC.

Keywords

clinical diagnostics
DNA methylation
episignatures
neurodevelopmental syndromes

Access to Document

10.1002/humu.24446

FulltextAccepted author manuscript, 250 KB

Cite this

Levy, M. A., Relator, R., McConkey, H., Pranckeviciene, E., Kerkhof, J., Barat-Houari, M., Bargiacchi, S., Biamino, E., Palomares Bralo, M., Cappuccio, G., Ciolfi, A., Clarke, A., DuPont, B. R., Elting, M. W., Faivre, L., Fee, T., Ferilli, M., Fletcher, R. S., Cherick, F., ... Sadikovic, B. (2022). Functional correlation of genome-wide DNA methylation profiles in genetic neurodevelopmental disorders. Human Mutation, 43(11), 1609-1628. https://doi.org/10.1002/humu.24446

Functional correlation of genome-wide DNA methylation profiles in genetic neurodevelopmental disorders. / Levy, Michael A.; Relator, Raissa; McConkey, Haley; Pranckeviciene, Erinija; Kerkhof, Jennifer; Barat-Houari, Mouna; Bargiacchi, Sara; Biamino, Elisa; Palomares Bralo, María; Cappuccio, Gerarda; Ciolfi, Andrea; Clarke, Angus; DuPont, Barbara R.; Elting, Mariet W.; Faivre, Laurence; Fee, Timothy; Ferilli, Marco; Fletcher, Robin S.; Cherick, Florian; Foroutan, Aidin; Friez, Michael J.; Gervasini, Cristina; Haghshenas, Sadegheh; Hilton, Benjamin A.; Jenkins, Zandra; Kaur, Simranpreet; Lewis, Suzanne; Louie, Raymond J.; Maitz, Silvia; Milani, Donatella; Morgan, Angela T.; Oegema, Renske; Østergaard, Elsebet; Pallares, Nathalie R.; Piccione, Maria; Plomp, Astrid S.; Poulton, Cathryn; Reilly, Jack; Rius, Rocio; Robertson, Stephen; Rooney, Kathleen; Rousseau, Justine; Santen, Gijs W.E.; Santos-Simarro, Fernando; Schijns, Josephine; Squeo, Gabriella M.; John, Miya St; Thauvin-Robinet, Christel; Traficante, Giovanna; van der Sluijs, Pleuntje J.; Vergano, Samantha A.; Vos, Niels; Walden, Kellie K.; Azmanov, Dimitar; Balci, Tugce B.; Banka, Siddharth; Gecz, Jozef; Henneman, Peter; Lee, Jennifer A.; Mannens, Marcel M.A.M.; Roscioli, Tony; Siu, Victoria; Amor, David J.; Baynam, Gareth; Bend, Eric G.; Boycott, Kym; Brunetti-Pierri, Nicola; Campeau, Philippe M.; Campion, Dominique; Christodoulou, John; Dyment, David; Esber, Natacha; Fahrner, Jill A.; Fleming, Mark D.; Genevieve, David; Heron, Delphine; Husson, Thomas; Kernohan, Kristin D.; McNeill, Alisdair; Menke, Leonie A.; Merla, Giuseppe; Prontera, Paolo; Rockman-Greenberg, Cheryl; Schwartz, Charles; Skinner, Steven A.; Stevenson, Roger E.; Vincent, Marie; Vitobello, Antonio; Tartaglia, Marco; Alders, Marielle; Tedder, Matthew L.; Sadikovic, Bekim.

In: Human Mutation, Vol. 43, No. 11, 2022, p. 1609-1628.

Research output: Contribution to journal › Journal article › Research › peer-review

Levy, MA, Relator, R, McConkey, H, Pranckeviciene, E, Kerkhof, J, Barat-Houari, M, Bargiacchi, S, Biamino, E, Palomares Bralo, M, Cappuccio, G, Ciolfi, A, Clarke, A, DuPont, BR, Elting, MW, Faivre, L, Fee, T, Ferilli, M, Fletcher, RS, Cherick, F, Foroutan, A, Friez, MJ, Gervasini, C, Haghshenas, S, Hilton, BA, Jenkins, Z, Kaur, S, Lewis, S, Louie, RJ, Maitz, S, Milani, D, Morgan, AT, Oegema, R, Østergaard, E, Pallares, NR, Piccione, M, Plomp, AS, Poulton, C, Reilly, J, Rius, R, Robertson, S, Rooney, K, Rousseau, J, Santen, GWE, Santos-Simarro, F, Schijns, J, Squeo, GM, John, MS, Thauvin-Robinet, C, Traficante, G, van der Sluijs, PJ, Vergano, SA, Vos, N, Walden, KK, Azmanov, D, Balci, TB, Banka, S, Gecz, J, Henneman, P, Lee, JA, Mannens, MMAM, Roscioli, T, Siu, V, Amor, DJ, Baynam, G, Bend, EG, Boycott, K, Brunetti-Pierri, N, Campeau, PM, Campion, D, Christodoulou, J, Dyment, D, Esber, N, Fahrner, JA, Fleming, MD, Genevieve, D, Heron, D, Husson, T, Kernohan, KD, McNeill, A, Menke, LA, Merla, G, Prontera, P, Rockman-Greenberg, C, Schwartz, C, Skinner, SA, Stevenson, RE, Vincent, M, Vitobello, A, Tartaglia, M, Alders, M, Tedder, ML & Sadikovic, B 2022, 'Functional correlation of genome-wide DNA methylation profiles in genetic neurodevelopmental disorders', Human Mutation, vol. 43, no. 11, pp. 1609-1628. https://doi.org/10.1002/humu.24446

Levy, Michael A. ; Relator, Raissa ; McConkey, Haley ; Pranckeviciene, Erinija ; Kerkhof, Jennifer ; Barat-Houari, Mouna ; Bargiacchi, Sara ; Biamino, Elisa ; Palomares Bralo, María ; Cappuccio, Gerarda ; Ciolfi, Andrea ; Clarke, Angus ; DuPont, Barbara R. ; Elting, Mariet W. ; Faivre, Laurence ; Fee, Timothy ; Ferilli, Marco ; Fletcher, Robin S. ; Cherick, Florian ; Foroutan, Aidin ; Friez, Michael J. ; Gervasini, Cristina ; Haghshenas, Sadegheh ; Hilton, Benjamin A. ; Jenkins, Zandra ; Kaur, Simranpreet ; Lewis, Suzanne ; Louie, Raymond J. ; Maitz, Silvia ; Milani, Donatella ; Morgan, Angela T. ; Oegema, Renske ; Østergaard, Elsebet ; Pallares, Nathalie R. ; Piccione, Maria ; Plomp, Astrid S. ; Poulton, Cathryn ; Reilly, Jack ; Rius, Rocio ; Robertson, Stephen ; Rooney, Kathleen ; Rousseau, Justine ; Santen, Gijs W.E. ; Santos-Simarro, Fernando ; Schijns, Josephine ; Squeo, Gabriella M. ; John, Miya St ; Thauvin-Robinet, Christel ; Traficante, Giovanna ; van der Sluijs, Pleuntje J. ; Vergano, Samantha A. ; Vos, Niels ; Walden, Kellie K. ; Azmanov, Dimitar ; Balci, Tugce B. ; Banka, Siddharth ; Gecz, Jozef ; Henneman, Peter ; Lee, Jennifer A. ; Mannens, Marcel M.A.M. ; Roscioli, Tony ; Siu, Victoria ; Amor, David J. ; Baynam, Gareth ; Bend, Eric G. ; Boycott, Kym ; Brunetti-Pierri, Nicola ; Campeau, Philippe M. ; Campion, Dominique ; Christodoulou, John ; Dyment, David ; Esber, Natacha ; Fahrner, Jill A. ; Fleming, Mark D. ; Genevieve, David ; Heron, Delphine ; Husson, Thomas ; Kernohan, Kristin D. ; McNeill, Alisdair ; Menke, Leonie A. ; Merla, Giuseppe ; Prontera, Paolo ; Rockman-Greenberg, Cheryl ; Schwartz, Charles ; Skinner, Steven A. ; Stevenson, Roger E. ; Vincent, Marie ; Vitobello, Antonio ; Tartaglia, Marco ; Alders, Marielle ; Tedder, Matthew L. ; Sadikovic, Bekim. / Functional correlation of genome-wide DNA methylation profiles in genetic neurodevelopmental disorders. In: Human Mutation. 2022 ; Vol. 43, No. 11. pp. 1609-1628.

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title = "Functional correlation of genome-wide DNA methylation profiles in genetic neurodevelopmental disorders",

abstract = "An expanding range of genetic syndromes are characterized by genome-wide disruptions in DNA methylation profiles referred to as episignatures. Episignatures are distinct, highly sensitive, and specific biomarkers that have recently been applied in clinical diagnosis of genetic syndromes. Episignatures are contained within the broader disorder-specific genome-wide DNA methylation changes, which can share significant overlap among different conditions. In this study, we performed functional genomic assessment and comparison of disorder-specific and overlapping genome-wide DNA methylation changes related to 65 genetic syndromes with previously described episignatures. We demonstrate evidence of disorder-specific and recurring genome-wide differentially methylated probes (DMPs) and regions (DMRs). The overall distribution of DMPs and DMRs across the majority of the neurodevelopmental genetic syndromes analyzed showed substantial enrichment in gene promoters and CpG islands, and under-representation of the more variable intergenic regions. Analysis showed significant enrichment of the DMPs and DMRs in gene pathways and processes related to neurodevelopment, including neurogenesis, synaptic signaling and synaptic transmission. This study expands beyond the diagnostic utility of DNA methylation episignatures by demonstrating correlation between the function of the mutated genes and the consequent genomic DNA methylation profiles as a key functional element in the molecular etiology of genetic neurodevelopmental disorders.",

keywords = "clinical diagnostics, DNA methylation, episignatures, neurodevelopmental syndromes",

author = "Levy, {Michael A.} and Raissa Relator and Haley McConkey and Erinija Pranckeviciene and Jennifer Kerkhof and Mouna Barat-Houari and Sara Bargiacchi and Elisa Biamino and {Palomares Bralo}, Mar{\'i}a and Gerarda Cappuccio and Andrea Ciolfi and Angus Clarke and DuPont, {Barbara R.} and Elting, {Mariet W.} and Laurence Faivre and Timothy Fee and Marco Ferilli and Fletcher, {Robin S.} and Florian Cherick and Aidin Foroutan and Friez, {Michael J.} and Cristina Gervasini and Sadegheh Haghshenas and Hilton, {Benjamin A.} and Zandra Jenkins and Simranpreet Kaur and Suzanne Lewis and Louie, {Raymond J.} and Silvia Maitz and Donatella Milani and Morgan, {Angela T.} and Renske Oegema and Elsebet {\O}stergaard and Pallares, {Nathalie R.} and Maria Piccione and Plomp, {Astrid S.} and Cathryn Poulton and Jack Reilly and Rocio Rius and Stephen Robertson and Kathleen Rooney and Justine Rousseau and Santen, {Gijs W.E.} and Fernando Santos-Simarro and Josephine Schijns and Squeo, {Gabriella M.} and John, {Miya St} and Christel Thauvin-Robinet and Giovanna Traficante and {van der Sluijs}, {Pleuntje J.} and Vergano, {Samantha A.} and Niels Vos and Walden, {Kellie K.} and Dimitar Azmanov and Balci, {Tugce B.} and Siddharth Banka and Jozef Gecz and Peter Henneman and Lee, {Jennifer A.} and Mannens, {Marcel M.A.M.} and Tony Roscioli and Victoria Siu and Amor, {David J.} and Gareth Baynam and Bend, {Eric G.} and Kym Boycott and Nicola Brunetti-Pierri and Campeau, {Philippe M.} and Dominique Campion and John Christodoulou and David Dyment and Natacha Esber and Fahrner, {Jill A.} and Fleming, {Mark D.} and David Genevieve and Delphine Heron and Thomas Husson and Kernohan, {Kristin D.} and Alisdair McNeill and Menke, {Leonie A.} and Giuseppe Merla and Paolo Prontera and Cheryl Rockman-Greenberg and Charles Schwartz and Skinner, {Steven A.} and Stevenson, {Roger E.} and Marie Vincent and Antonio Vitobello and Marco Tartaglia and Marielle Alders and Tedder, {Matthew L.} and Bekim Sadikovic",

note = "Publisher Copyright: {\textcopyright} 2022 Wiley Periodicals LLC.",

year = "2022",

doi = "10.1002/humu.24446",

language = "English",

volume = "43",

pages = "1609--1628",

journal = "Human Mutation",

issn = "1059-7794",

publisher = "JohnWiley & Sons, Inc.",

number = "11",

}

TY - JOUR

T1 - Functional correlation of genome-wide DNA methylation profiles in genetic neurodevelopmental disorders

AU - Levy, Michael A.

AU - Relator, Raissa

AU - McConkey, Haley

AU - Pranckeviciene, Erinija

AU - Kerkhof, Jennifer

AU - Barat-Houari, Mouna

AU - Bargiacchi, Sara

AU - Biamino, Elisa

AU - Palomares Bralo, María

AU - Cappuccio, Gerarda

AU - Ciolfi, Andrea

AU - Clarke, Angus

AU - DuPont, Barbara R.

AU - Elting, Mariet W.

AU - Faivre, Laurence

AU - Fee, Timothy

AU - Ferilli, Marco

AU - Fletcher, Robin S.

AU - Cherick, Florian

AU - Foroutan, Aidin

AU - Friez, Michael J.

AU - Gervasini, Cristina

AU - Haghshenas, Sadegheh

AU - Hilton, Benjamin A.

AU - Jenkins, Zandra

AU - Kaur, Simranpreet

AU - Lewis, Suzanne

AU - Louie, Raymond J.

AU - Maitz, Silvia

AU - Milani, Donatella

AU - Morgan, Angela T.

AU - Oegema, Renske

AU - Østergaard, Elsebet

AU - Pallares, Nathalie R.

AU - Piccione, Maria

AU - Plomp, Astrid S.

AU - Poulton, Cathryn

AU - Reilly, Jack

AU - Rius, Rocio

AU - Robertson, Stephen

AU - Rooney, Kathleen

AU - Rousseau, Justine

AU - Santen, Gijs W.E.

AU - Santos-Simarro, Fernando

AU - Schijns, Josephine

AU - Squeo, Gabriella M.

AU - John, Miya St

AU - Thauvin-Robinet, Christel

AU - Traficante, Giovanna

AU - van der Sluijs, Pleuntje J.

AU - Vergano, Samantha A.

AU - Vos, Niels

AU - Walden, Kellie K.

AU - Azmanov, Dimitar

AU - Balci, Tugce B.

AU - Banka, Siddharth

AU - Gecz, Jozef

AU - Henneman, Peter

AU - Lee, Jennifer A.

AU - Mannens, Marcel M.A.M.

AU - Roscioli, Tony

AU - Siu, Victoria

AU - Amor, David J.

AU - Baynam, Gareth

AU - Bend, Eric G.

AU - Boycott, Kym

AU - Brunetti-Pierri, Nicola

AU - Campeau, Philippe M.

AU - Campion, Dominique

AU - Christodoulou, John

AU - Dyment, David

AU - Esber, Natacha

AU - Fahrner, Jill A.

AU - Fleming, Mark D.

AU - Genevieve, David

AU - Heron, Delphine

AU - Husson, Thomas

AU - Kernohan, Kristin D.

AU - McNeill, Alisdair

AU - Menke, Leonie A.

AU - Merla, Giuseppe

AU - Prontera, Paolo

AU - Rockman-Greenberg, Cheryl

AU - Schwartz, Charles

AU - Skinner, Steven A.

AU - Stevenson, Roger E.

AU - Vincent, Marie

AU - Vitobello, Antonio

AU - Tartaglia, Marco

AU - Alders, Marielle

AU - Tedder, Matthew L.

AU - Sadikovic, Bekim

PY - 2022

Y1 - 2022

N2 - An expanding range of genetic syndromes are characterized by genome-wide disruptions in DNA methylation profiles referred to as episignatures. Episignatures are distinct, highly sensitive, and specific biomarkers that have recently been applied in clinical diagnosis of genetic syndromes. Episignatures are contained within the broader disorder-specific genome-wide DNA methylation changes, which can share significant overlap among different conditions. In this study, we performed functional genomic assessment and comparison of disorder-specific and overlapping genome-wide DNA methylation changes related to 65 genetic syndromes with previously described episignatures. We demonstrate evidence of disorder-specific and recurring genome-wide differentially methylated probes (DMPs) and regions (DMRs). The overall distribution of DMPs and DMRs across the majority of the neurodevelopmental genetic syndromes analyzed showed substantial enrichment in gene promoters and CpG islands, and under-representation of the more variable intergenic regions. Analysis showed significant enrichment of the DMPs and DMRs in gene pathways and processes related to neurodevelopment, including neurogenesis, synaptic signaling and synaptic transmission. This study expands beyond the diagnostic utility of DNA methylation episignatures by demonstrating correlation between the function of the mutated genes and the consequent genomic DNA methylation profiles as a key functional element in the molecular etiology of genetic neurodevelopmental disorders.

AB - An expanding range of genetic syndromes are characterized by genome-wide disruptions in DNA methylation profiles referred to as episignatures. Episignatures are distinct, highly sensitive, and specific biomarkers that have recently been applied in clinical diagnosis of genetic syndromes. Episignatures are contained within the broader disorder-specific genome-wide DNA methylation changes, which can share significant overlap among different conditions. In this study, we performed functional genomic assessment and comparison of disorder-specific and overlapping genome-wide DNA methylation changes related to 65 genetic syndromes with previously described episignatures. We demonstrate evidence of disorder-specific and recurring genome-wide differentially methylated probes (DMPs) and regions (DMRs). The overall distribution of DMPs and DMRs across the majority of the neurodevelopmental genetic syndromes analyzed showed substantial enrichment in gene promoters and CpG islands, and under-representation of the more variable intergenic regions. Analysis showed significant enrichment of the DMPs and DMRs in gene pathways and processes related to neurodevelopment, including neurogenesis, synaptic signaling and synaptic transmission. This study expands beyond the diagnostic utility of DNA methylation episignatures by demonstrating correlation between the function of the mutated genes and the consequent genomic DNA methylation profiles as a key functional element in the molecular etiology of genetic neurodevelopmental disorders.

KW - clinical diagnostics

KW - DNA methylation

KW - episignatures

KW - neurodevelopmental syndromes

U2 - 10.1002/humu.24446

DO - 10.1002/humu.24446

M3 - Journal article

C2 - 35904121

AN - SCOPUS:85136511967

VL - 43

SP - 1609

EP - 1628

JO - Human Mutation

JF - Human Mutation

SN - 1059-7794

IS - 11

ER -