POLI HARLOWE, MARIA CECILIA BERTA

POLI HARLOWE, MARIA CECILIA BERTA

Preferred name

POLI HARLOWE, MARIA CECILIA BERTA

Main Affiliation

Facultad de Medicina Clínica Alemana Universidad del Desarrollo

Email

mpoli@alemana.cl

ORCID

0000-0001-6817-0573

Scopus Author ID

57214078113

Research Output

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Now showing 1 - 8 of 8

Publication

Clinical, neuroimaging, and molecular spectrum of TECPR2 ‐associated hereditary sensory and autonomic neuropathy with intellectual disability

2021 , Sonja Neuser , Barbara Brechmann , Gali Heimer , Ines Brösse , Susanna Schubert , Lauren O'Grady , Michael Zech , Siddharth Srivastava , David A. Sweetser , Yasemin Dincer , Volker Mall , Juliane Winkelmann , Christian Behrends , Basil T. Darras , Robert J. Graham , Parul Jayakar , Barry Byrne , Bat El Bar‐Aluma , Yael Haberman , Amir Szeinberg , Hesham M. Aldhalaan , Mais Hashem , Amal Al Tenaiji , Omar Ismayl , Asma E. Al Nuaimi , Karima Maher , Shahnaz Ibrahim , Fatima Khan , Henry Houlden , Vijayalakshmi S. Ramakumaran , Alistair T. Pagnamenta , Jennifer E. Posey , James R. Lupski , Wen‐Hann Tan , Gehad ElGhazali , Isabella Herman , Tatiana Muñoz , REPETTO LISBOA, MARIA GABRIELA , Angelika Seitz , Mandy Krumbiegel , POLI HARLOWE, MARIA CECILIA BERTA , Usha Kini , Stephanie Efthymiou , Jens Meiler , Reza Maroofian , Fowzan S. Alkuraya , Rami Abou Jamra , Bernt Popp , Bruria Ben‐Zeev , Darius Ebrahimi‐Fakhari

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Publication

Absent B cells, agammaglobulinemia, and hypertrophic cardiomyopathy in folliculin-interacting protein 1 deficiency

2021 , Francesco Saettini , POLI HARLOWE, MARIA CECILIA BERTA , Jaime Vengoechea , Sonia Bonanomi , Julio C. Orellana , Grazia Fazio , Fred H. Rodriguez , Loreani P. Noguera , Claire Booth , Valentina Jarur-Chamy , Marissa Shams , Maria Iascone , Maja Vukic , Serena Gasperini , Manuel Quadri , Amairelys Barroeta Seijas , Elizabeth Rivers , Mario Mauri , Raffaele Badolato , Gianni Cazzaniga , Cristina Bugarin , Giuseppe Gaipa , Wilma G. M. Kroes , Daniele Moratto , Monique M. van Oostaijen-ten Dam , Frank Baas , Silvère van der Maarel , Rocco Piazza , Zeynep H. Coban-Akdemir , James R. Lupski , Bo Yuan , Ivan K. Chinn , Lucia Daxinger , Andrea Biondi

Abstract Agammaglobulinemia is the most profound primary antibody deficiency that can occur due to an early termination of B-cell development. We here investigated 3 novel patients, including the first known adult, from unrelated families with agammaglobulinemia, recurrent infections, and hypertrophic cardiomyopathy (HCM). Two of them also presented with intermittent or severe chronic neutropenia. We identified homozygous or compound-heterozygous variants in the gene for folliculin interacting protein 1 (FNIP1), leading to loss of the FNIP1 protein. B-cell metabolism, including mitochondrial numbers and activity and phosphatidylinositol 3-kinase/AKT pathway, was impaired. These defects recapitulated the Fnip1−/− animal model. Moreover, we identified either uniparental disomy or copy-number variants (CNVs) in 2 patients, expanding the variant spectrum of this novel inborn error of immunity. The results indicate that FNIP1 deficiency can be caused by complex genetic mechanisms and support the clinical utility of exome sequencing and CNV analysis in patients with broad phenotypes, including agammaglobulinemia and HCM. FNIP1 deficiency is a novel inborn error of immunity characterized by early and severe B-cell development defect, agammaglobulinemia, variable neutropenia, and HCM. Our findings elucidate a functional and relevant role of FNIP1 in B-cell development and metabolism and potentially neutrophil activity.

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Publication

Heterozygous Truncating Variants in POMP Escape Nonsense-Mediated Decay and Cause a Unique Immune Dysregulatory Syndrome

2018 , POLI HARLOWE, MARIA CECILIA BERTA , Frédéric Ebstein , Sarah K. Nicholas , Marietta M. de Guzman , Lisa R. Forbes , Ivan K. Chinn , Emily M. Mace , Tiphanie P. Vogel , Alexandre F. Carisey , BENAVIDES GONZALEZ, FELIPE ORLANDO , Zeynep H. Coban-Akdemir , Richard A. Gibbs , Shalini N. Jhangiani , Donna M. Muzny , Claudia M.B. Carvalho , Deborah A. Schady , Mahim Jain , Jill A. Rosenfeld , Lisa Emrick , Richard A. Lewis , Brendan Lee , Barbara A. Zieba , Sébastien Küry , Elke Krüger , James R. Lupski , Bret L. Bostwick , Jordan S. Orange

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Publication

Decoding complex inherited phenotypes in rare disorders: the DECIPHERD initiative for rare undiagnosed diseases in Chile

2024 , POLI HARLOWE, MARIA CECILIA BERTA , Boris Rebolledo-Jaramillo , Catalina Lagos , Joan Orellana , Gabriela Moreno , Luz M. Martín , Gonzalo Encina , Daniela Böhme , Víctor Faundes , M. Jesús Zavala , María Trinidad Hasbún , Sara Fischer , Florencia Brito , Diego Araya , Manuel Lira , Javiera de la Cruz , Camila Astudillo , Guillermo Lay-Son , Carolina Cares , Mariana Aracena , Esteban San Martin , Zeynep Coban-Akdemir , Jennifer E. Posey , James R. Lupski , Gabriela M. Repetto

AbstractRare diseases affect millions of people worldwide, and most have a genetic etiology. The incorporation of next-generation sequencing into clinical settings, particularly exome and genome sequencing, has resulted in an unprecedented improvement in diagnosis and discovery in the past decade. Nevertheless, these tools are unavailable in many countries, increasing health care gaps between high- and low-and-middle-income countries and prolonging the “diagnostic odyssey” for patients. To advance genomic diagnoses in a setting of limited genomic resources, we developed DECIPHERD, an undiagnosed diseases program in Chile. DECIPHERD was implemented in two phases: training and local development. The training phase relied on international collaboration with Baylor College of Medicine, and the local development was structured as a hybrid model, where clinical and bioinformatics analysis were performed in-house and sequencing outsourced abroad, due to lack of high-throughput equipment in Chile. We describe the implementation process and findings of the first 103 patients. They had heterogeneous phenotypes, including congenital anomalies, intellectual disabilities and/or immune system dysfunction. Patients underwent clinical exome or research exome sequencing, as solo cases or with parents using a trio design. We identified pathogenic, likely pathogenic or variants of unknown significance in genes related to the patients´ phenotypes in 47 (45.6%) of them. Half were de novo informative variants, and half of the identified variants have not been previously reported in public databases. DECIPHERD ended the diagnostic odyssey for many participants. This hybrid strategy may be useful for settings of similarly limited genomic resources and lead to discoveries in understudied populations.

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Publication

Novel Heterozygous Mutation in NFKB2 Is Associated With Early Onset CVID and a Functional Defect in NK Cells Complicated by Disseminated CMV Infection and Severe Nephrotic Syndrome

2019 , Alejandra Aird , Macarena Lagos , Alexander Vargas-Hernández , Jennifer E. Posey , Zeynep Coban-Akdemir , Shalini Jhangiani , Emily M. Mace , Anaid Reyes , Alejandra King , Felipe Cavagnaro , Lisa R. Forbes , Ivan K. Chinn , James R. Lupski , Jordan S. Orange , POLI HARLOWE, MARIA CECILIA BERTA

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Publication

HEM1 deficiency disrupts mTORC2 and F-actin control in inherited immunodysregulatory disease

2020 , Sarah A. Cook , William A. Comrie , POLI HARLOWE, MARIA CECILIA BERTA , Morgan Similuk , Andrew J. Oler , Aiman J. Faruqi , Douglas B. Kuhns , Sheng Yang , Alexander Vargas-Hernández , Alexandre F. Carisey , Benjamin Fournier , D. Eric Anderson , Susan Price , Margery Smelkinson , Wadih Abou Chahla , Lisa R. Forbes , Emily M. Mace , Tram N. Cao , Zeynep H. Coban-Akdemir , Shalini N. Jhangiani , Donna M. Muzny , Richard A. Gibbs , James R. Lupski , Jordan S. Orange , Geoffrey D. E. Cuvelier , Moza Al Hassani , Nawal Al Kaabi , Zain Al Yafei , Soma Jyonouchi , Nikita Raje , Jason W. Caldwell , Yanping Huang , Janis K. Burkhardt , Sylvain Latour , Baoyu Chen , Gehad ElGhazali , V. Koneti Rao , Ivan K. Chinn , Michael J. Lenardo

An inherited disorder makes WAVEs The WAVE regulatory complex (WRC) is a multiunit complex that regulates actin cytoskeleton formation. Although other actin-regulatory proteins modulate human immune responses, the precise role for the WRC has not yet been established. Cook et al. studied five patients from four unrelated families who harbor missense variants of the gene encoding the WRC component HEM1. These patients presented with recurrent infections and poor antibody responses, along with enhanced allergic and autoimmune disorders. HEM1 was found to be required for the regulation of cortical actin and granule release in T cells and also interacted with a key metabolic signaling complex contributing to the disease phenotype. By linking these interactions to immune function, this work suggests potential targets for future immunotherapies. Science , this issue p. 202

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Publication

Genetic and mechanistic diversity in pediatric hemophagocytic lymphohistiocytosis

2018 , Ivan K. Chinn , Olive S. Eckstein , Erin C. Peckham-Gregory , Baruch R. Goldberg , Lisa R. Forbes , Sarah K. Nicholas , Emily M. Mace , Tiphanie P. Vogel , Harshal A. Abhyankar , Maria I. Diaz , Helen E. Heslop , Robert A. Krance , Caridad A. Martinez , Trung C. Nguyen , Dalia A. Bashir , Jordana R. Goldman , Asbjørg Stray-Pedersen , Luis A. Pedroza , POLI HARLOWE, MARIA CECILIA BERTA , Juan C. Aldave-Becerra , Sean A. McGhee , Waleed Al-Herz , Aghiad Chamdin , Zeynep H. Coban-Akdemir , Shalini N. Jhangiani , Donna M. Muzny , Tram N. Cao , Diana N. Hong , Richard A. Gibbs , James R. Lupski , Jordan S. Orange , Kenneth L. McClain , Carl E. Allen

Key Points Whole-exome sequencing may identify specific therapeutic opportunities for patients with HLH. HLH should be conceptualized as a critical illness phenotype driven by toxic activation of immune cells from different underlying mechanisms.

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Publication

Identifying Genes Whose Mutant Transcripts Cause Dominant Disease Traits by Potential Gain-of-Function Alleles

2018 , Zeynep Coban-Akdemir , Janson J. White , Xiaofei Song , Shalini N. Jhangiani , Jawid M. Fatih , Tomasz Gambin , Yavuz Bayram , Ivan K. Chinn , Ender Karaca , Jaya Punetha , Cecilia Poli , Eric Boerwinkle , Chad A. Shaw , Jordan S. Orange , Richard A. Gibbs , Tuuli Lappalainen , James R. Lupski , Claudia M.B. Carvalho

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POLI HARLOWE, MARIA CECILIA BERTA

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Clinical, neuroimaging, and molecular spectrum of TECPR2 ‐associated hereditary sensory and autonomic neuropathy with intellectual disability

Absent B cells, agammaglobulinemia, and hypertrophic cardiomyopathy in folliculin-interacting protein 1 deficiency

Heterozygous Truncating Variants in POMP Escape Nonsense-Mediated Decay and Cause a Unique Immune Dysregulatory Syndrome

Decoding complex inherited phenotypes in rare disorders: the DECIPHERD initiative for rare undiagnosed diseases in Chile

Novel Heterozygous Mutation in NFKB2 Is Associated With Early Onset CVID and a Functional Defect in NK Cells Complicated by Disseminated CMV Infection and Severe Nephrotic Syndrome

HEM1 deficiency disrupts mTORC2 and F-actin control in inherited immunodysregulatory disease

Genetic and mechanistic diversity in pediatric hemophagocytic lymphohistiocytosis

Identifying Genes Whose Mutant Transcripts Cause Dominant Disease Traits by Potential Gain-of-Function Alleles

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POLI HARLOWE, MARIA CECILIA BERTA

Research Output

Filters

Author

Organization

Has files

Type

Settings

Sort By

Results per page

Clinical, neuroimaging, and molecular spectrum of TECPR2 ‐associated hereditary sensory and autonomic neuropathy with intellectual disability

Absent B cells, agammaglobulinemia, and hypertrophic cardiomyopathy in folliculin-interacting protein 1 deficiency

Heterozygous Truncating Variants in POMP Escape Nonsense-Mediated Decay and Cause a Unique Immune Dysregulatory Syndrome

Decoding complex inherited phenotypes in rare disorders: the DECIPHERD initiative for rare undiagnosed diseases in Chile

Novel Heterozygous Mutation in NFKB2 Is Associated With Early Onset CVID and a Functional Defect in NK Cells Complicated by Disseminated CMV Infection and Severe Nephrotic Syndrome

HEM1 deficiency disrupts mTORC2 and F-actin control in inherited immunodysregulatory disease

Genetic and mechanistic diversity in pediatric hemophagocytic lymphohistiocytosis

Identifying Genes Whose Mutant Transcripts Cause Dominant Disease Traits by Potential Gain-of-Function Alleles

Sede Santiago

Sede Concepción