Article
Immunology
Nikita R. Raje, Janelle R. Noel-MacDonnell, Katherine A. Shortt, Nicole M. Gigliotti, Marcia A. Chan, Daniel P. Heruth
Summary: The phenotypic variations of chromosome 22q11.2 deletion syndrome (22qDS) are not well explained. This study investigated gene expression in T cells of individuals with and without 22qDS, and found differentially expressed genes associated with T cell counts and markers. This suggests an important role of T cells in defective communication in 22qDS.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Pratibha Bhalla, Qiumei Du, Ashwani Kumar, Chao Xing, Angela Moses, Igor Dozmorov, Christian A. Wysocki, Ondine B. Cleaver, Timothy J. Pirolli, Mary Louise Markert, Maria Teresa de la Morena, Antonio Baldini, Nicolai S. C. van Ders
Summary: 22q11.2 deletion syndrome (22q11.2DS) is the most common human chromosomal microdeletion, causing thymic hypoplasia and T cell lymphopenia. This study identified that abnormal thymic mesenchymal cells were responsible for the small size of the embryonic thymuses in the 22q11.2DS mouse models, and this could be corrected by replacing them with normal mesenchyme.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Review
Pediatrics
Carolina Putotto, Flaminia Pugnaloni, Marta Unolt, Stella Maiolo, Matteo Trezzi, Maria Cristina Digilio, Annapaola Cirillo, Giuseppe Limongelli, Bruno Marino, Giulio Calcagni, Paolo Versacci
Summary: This review examines the cardiac outcome and surgical prognosis of patients with 22q11.2 deletion syndrome, focusing on conotruncal heart defects. The impact of genetic aspects, comorbidities, and anatomical features on cardiac surgical treatment is highlighted.
Article
Biochemistry & Molecular Biology
Elizabeth M. Paronett, Corey A. Bryan, Megan E. Maynard, Julia A. Goroff, Daniel W. Meechan, Anthony-Samuel LaMantia, Thomas M. Maynard
Summary: Facial dysmorphology is a hallmark of 22q11.2 deletion syndrome. The gene Ranbp1, which mediates nucleocytoplasmic protein trafficking, is a key player in craniofacial development. Mutations in Ranbp1 lead to facial phenotypes, particularly in the midline facial skeleton.
HUMAN MOLECULAR GENETICS
(2023)
Article
Biology
Sara Ciof, Gemma Flore, Stefania Martucciello, Marchesa Bilio, Maria Giuseppina Turturo, Elizabeth Illingworth
Summary: The loss of a single copy of TBX1 accounts for most of the clinical signs and symptoms of 22q11.2 deletion syndrome. The main function of TBX1 in the mouse brain is to suppress vessel branching morphogenesis through regulation of Vegfr3. Inactivating Vegfr3 enhances brain vessel branching and filopodia formation, while increasing Vegfr3 expression fully rescues these phenotypes.
LIFE SCIENCE ALLIANCE
(2022)
Article
Neurosciences
Ilaria Favicchia, Gemma Flore, Sara Cioffi, Gabriella Lania, Antonio Baldini, Elizabeth Illingworth
Summary: This research identified two FDA-approved drugs, Tranylcypromine and Vitamin B12, which successfully rescued cortical abnormalities in Tbx1 mutant mice. The rescue was achieved through mechanisms independent of Tbx1 function, suggesting potential importance for targeting specific genes within the deleted 22q11.2 region for effective treatments.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Neha Paranjape, Yu-Hsiu T. Lin, Quetzal Flores-Ramirez, Vishesh Sarin, Amanda Brooke Johnson, Julia Chu, Mercedes Paredes, Arun P. Wiita
Summary: This article describes a method of applying the gene cloning engineering technique to induced pluripotent stem cell models for studying different gene deletions associated with 22q11.2 deletion syndrome. Analysis using transcriptomics and cell surface proteomics reveals deletion-associated alterations in neuronal proliferation and adhesion, and implantation of neuronal progenitor cells into the cortex of neonatal mice shows potential effects on neuronal maturation. These isogenic models provide a unique resource to study this less-common variant of 22q11.2 deletion syndrome.
SCIENTIFIC REPORTS
(2023)
Article
Pediatrics
William N. N. Evans, Ruben J. J. Acherman, Humberto Restrepo
Summary: We reviewed patients with chromosome 22q11.2 deletion syndrome and analyzed cardiovascular findings in live-born patients in Nevada between March 2007 and September 2020. Out of 60 identified patients, 53% were female and 80% had conotruncal abnormalities. Males were statistically more likely to have a right aortic arch than females.
CLINICAL PEDIATRICS
(2023)
Article
Genetics & Heredity
Tracy Heung, Brigid Conroy, Sarah Malecki, Joanne Ha, Erik Boot, Maria Corral, Anne S. Bassett
Summary: 22q11.2 deletion syndrome affects final adult height distribution, with around 22.7% of patients having short stature, a significantly higher rate than expected in the general population. Factors such as moderate-to-severe intellectual disability, major congenital heart disease, and the common LCR22A-LCR22D (A-D) deletion are independent risk factors for short stature.
Article
Obstetrics & Gynecology
Giovanna Irene Battistoni, Giovanni Delli Carpini, Massimo Colaneri, Ramona Montironi, Giulia Gelzoni, Luca Giannella, Stefano Raffaele Giannubilo, Marco Pozzi, Andrea Ciavattini
Summary: This study aimed to validate the Thymic-Thoracic Ratio as a sonographic marker for conotruncal defects and investigate its correlation with the severity of these defects. The results showed that the T-T ratio had good diagnostic performance in identifying conotruncal defects and was negatively correlated with the Aristotle score.
JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
(2022)
Article
Pediatrics
Ella Nissan, Uriel Katz, Yael Levy-Shraga, Shirly Frizinsky, Eldar Carmel, Doron Gothelf, Raz Somech
Summary: This study evaluated clinical aspects of patients with DiGeorge syndrome and found that common symptoms included congenital heart defects, speech delay, and recurrent infections. Some patients also had anemia and thrombocytopenia. Patients with T cell deficiencies were more prone to recurrent chest infections.
JOURNAL OF PEDIATRICS
(2021)
Article
Immunology
Zhe Zhang, LiHua Shi, Li Song, Kelly Maurer, Xue Zhao, Elaine H. Zackai, Daniel E. McGinn, T. Blaine Crowley, Donna M. McDonald McGinn, Kathleen E. Sullivan
Summary: Chromosome 22q11.2 deletion syndrome is a common inborn error of immunity often characterized by low T cell numbers and later complications such as atopy and autoimmunity. This study found altered CD4 T cell chromatin in individuals with 22q11.2 deletion, reflecting qualitative changes that may contribute to the disease mechanism alongside the known quantitative defects.
JOURNAL OF CLINICAL IMMUNOLOGY
(2021)
Article
Otorhinolaryngology
Nathan Lu, Alexa J. J. Kacin, Amber D. D. Shaffer, Amanda L. L. Stapleton
Summary: This study investigates the occurrence and development of otologic and sinonasal disease in individuals with 22q11.2 deletion syndrome. The results show that around half of children with this syndrome require surgical management for these diseases. Further studies will focus on the role of immunodeficiency in otologic and rhinologic diseases in this population.
OTOLARYNGOLOGY-HEAD AND NECK SURGERY
(2023)
Article
Immunology
Nicolas Lundahl Ciano-Petersen, Omar Hamad-Cueto, Hania Drissi-Reyes, Alvaro Dona-Diaz, Guillermina Garcia-Martin
Summary: 22q11.2 deletion syndrome is characterized by specific clinical features such as heart abnormalities, thymus issues, palatal abnormalities, and hypocalcemia, as well as autoimmune and psychiatric disorders. Patients may experience psychotic disorders, developmental regression, and long-term cognitive disturbances. The syndrome may be linked to immune dysregulation and an increased prevalence of autoimmune disorders, potentially due to thymic abnormalities playing a role in self-tolerance.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Clinical Neurology
Michael Bayat, Allan Bayat
Summary: This article reviews the neurological manifestations of 22q11.2 deletion syndrome, including epilepsy, movement disorders, and abnormal neuroradiological findings. The syndrome is associated with increased incidence of various neurological disorders, as well as an increased risk of developing Parkinson's disease and dystonia. The risk of psychiatric disorders, particularly schizophrenia, is also significantly increased.
NEUROLOGICAL SCIENCES
(2022)
Article
Pediatrics
Shwetha Kuthiroly, Dhanya Yesodharan, Natasha Radhakrishnan, Aparna Ganapathy, Ashraf U. Mannan, Michael M. Hoffmann, Sheela Nampoothiri
Summary: This study analyzed the clinical and molecular spectrum of Lipoprotein Lipase deficiency, highlighting the importance of a strict low-fat diet in managing the disorder effectively.
INDIAN JOURNAL OF PEDIATRICS
(2021)
Letter
Clinical Neurology
Santhakumar Senthilvelan, Sathish Kandasamy, Ramshekhar N. Menon, Sheela Nampoothiri, Harikrishnan Ramachandran, Bejoy Thomas, Chandrasekharan Kesavadas
CLINICAL NEURORADIOLOGY
(2021)
Article
Genetics & Heredity
Smrithi Salian, Hind Benkerroum, Thi Tuyet Mai Nguyen, Sheela Nampoothiri, Taroh Kinoshita, Temis Maria Felix, Fiona Stewart, Sanjay M. Sisodiya, Yoshiko Murakami, Philippe M. Campeau
Summary: DOORS syndrome is a rare disorder characterized by a range of symptoms, including deafness, intellectual disability, and others. This study identified two individuals with DOORS syndrome but without deafness, both carrying a homozygous missense variant in the PIGF gene. The study highlights the variability of clinical features in DOORS syndrome and the importance of considering inherited GPI deficiencies in diagnosis.
Article
Multidisciplinary Sciences
Lila Allou, Sara Balzano, Andreas Magg, Mathieu Quinodoz, Beryl Royer-Bertrand, Robert Schopflin, Wing-Lee Chan, Carlos E. Speck-Martins, Daniel Rocha Carvalho, Luciano Farage, Charles Marques Lourenco, Regina Albuquerque, Srilakshmi Rajagopal, Sheela Nampoothiri, Belinda Campos-Xavier, Carole Chiesa, Florence Niel-Buetschi, Lars Wittler, Bernd Timmermann, Malte Spielmann, Michael I. Robson, Alessa Ringel, Verena Heinrich, Giulia Cova, Guillaume Andrey, Cesar A. Prada-Medina, Rosanna Pescini-Gobert, Sheila Unger, Luisa Bonafe, Phillip Grote, Carlo Rivolta, Stefan Mundlos, Andrea Superti-Furga
Summary: This study demonstrates that genetic ablation of a lncRNA locus on human chromosome 2 can result in a severe congenital limb malformation. The findings highlight the importance of the lncRNA locus in regulating En1 gene expression and controlling dorso-ventral polarity in the developing limb bud, leading to a specific subset of the En1-associated phenotype in human Mendelian disease.
Article
Clinical Neurology
Ratna Dua Puri, Nitika Setia, N. Vinu, Sujatha Jagadeesh, Sheela Nampoothiri, Neerja Gupta, Mamta Muranjan, Meenakshi Bhat, Katta M. Girisha, Madhulika Kabra, Jyotsna Verma, Divya C. Thomas, Ishpreet Biji, Jayarekha Raja, Ravinder Makkar, Ishwar C. Verma, Priya S. Kishnani
Summary: This study evaluated a cohort of Indian LOPD patients and found a more severe disease phenotype with higher prevalence of cardiac involvement compared to previous reports. The need to improve awareness and diagnosis of LOPD in India is emphasized.
NEUROMUSCULAR DISORDERS
(2021)
Article
Genetics & Heredity
Delfien Syx, Yoshihiro Ishikawa, Jan Gebauer, Sergei P. Boudko, Brecht Guillemyn, Tim Van Damme, Sanne D'hondt, Sofie Symoens, Sheela Nampoothiri, Douglas B. Gould, Ulrich Baumann, Hans Peter Bachinger, Fransiska Malfait
Summary: Osteogenesis imperfecta is caused by a homozygous p.(R222S) substitution in the HSP47 gene, resulting in significantly reduced affinity of HSP47-R222S for type I collagen and leading to overmodification of type I collagen. Unlike other types of OI, this overmodification is not due to prolonged exposure of collagen to modifying enzymes, as the intracellular folding rate of type I collagen appears to be normal. Abnormal binding of HSP47-R222S results in upregulation and increased binding of molecular chaperones and collagen-modifying enzymes, suggesting a compensatory mechanism for aberrant binding and eventually leading to overmodification of type I collagen chains.
Article
Genetics & Heredity
Amita Moirangthem, Kausik Mandal, Deepti Saxena, Priyanka Srivastava, Poonam Singh Gambhir, Neha Agrawal, Arya Shambhavi, Sheela Nampoothiri, Shubha R. Phadke
Summary: This study characterized the phenotypic and genotypic profiles of patients with overgrowth and intellectual disability (OGID), identifying aberrations in genes involved in epigenetic regulation and the PI3K-AKT pathway. NSD1-related Sotos syndrome was the most common disorder observed. Whole exome sequencing (ES) may have a higher diagnostic yield in patients with OGID compared to cytogenetic microarray (CMA).
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Review
Genetics & Heredity
Tibbe Dhooge, Tim Van Damme, Delfien Syx, Laura M. Mosquera, Sheela Nampoothiri, Anil Radhakrishnan, Pelin O. Simsek-Kiper, Gulen E. Utine, Maryse Bonduelle, Isabelle Migeotte, Osama Essawi, Serdar Ceylaner, Adila Al Kindy, Brad Tinkle, Sofie Symoens, Fransiska Malfait
Summary: Brittle cornea syndrome is a rare autosomal recessive disorder characterized by thin and fragile corneas that can lead to corneal rupture. Research on clinical and molecular features suggests its classification within the Ehlers-Danlos syndrome spectrum, and emphasizes the importance of genetic testing for timely diagnosis and prevention measures.
Review
Genetics & Heredity
Dominique P. Germain, Sergey Moiseev, Fernando Suarez-Obando, Faisal Al Ismaili, Huda Al Khawaja, Gheona Altarescu, Fellype C. Barreto, Farid Haddoum, Fatemeh Hadipour, Irina Maksimova, Mirelle Kramis, Sheela Nampoothiri, Khanh Ngoc Nguyen, Dau-Ming Niu, Juan Politei, Long-Sun Ro, Dung Vu Chi, Nan Chen, Sergey Kutsev
Summary: Family genetic testing is crucial for early diagnosis of patients with rare genetic diseases, but faces challenges in some countries due to barriers such as costs, awareness, and cultural factors.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Clinical Neurology
Pauline E. Schneeberger, Sheela Nampoothiri, Tess Holling, Dhanya Yesodharan, Malik Alawi, A. S. Knisely, Thomas Mueller, Barbara Plecko, Andreas R. Janecke, Kerstin Kutsche
Summary: GARP and EARP are membrane-tethering heterotetramers located at the trans-Golgi network and recycling endosomes, mediating retrograde transport and endocytic recycling. Patients with VPS50 variants exhibit severe developmental delay, microcephaly, seizures, and liver abnormalities.
Article
Biochemistry & Molecular Biology
Elena Botta, Arjan F. Theil, Anja Raams, Giuseppina Caligiuri, Sarah Giachetti, Silvia Bione, Maria Accadia, Anita Lombardi, Desiree E. C. Smith, Marisa Mendes, Sigrid M. A. Swagemakers, Peter J. Van der Spek, Gajja S. Salomons, Jan H. J. Hoeijmakers, Dhanya Yesodharan, Sheela Nampoothiri, Tomoo Ogi, Alan R. Lehmann, Donata Orioli, Wim Vermeulen
Summary: Trichothiodystrophy (TTD) is a rare hereditary neurodevelopmental disorder characterized by sulfur-deficient brittle hair, nails, and scaly skin, with highly variable clinical features. New gene defects have been identified to cause the non-photosensitive forms of TTD (NPS-TTD), impacting the stability of tRNA synthetases and protein translation. This study redefines TTD as a syndrome where proteins involved in gene expression are unstable, affecting both translation and transcription.
HUMAN MOLECULAR GENETICS
(2021)
Article
Endocrinology & Metabolism
Ana Soraya Palmira Dos Remedios Monteiro, Praveen Pavithran, Sheela Nampoothiri, Dhanya Yesodharan
Summary: A 36-year-old male presented with young-onset diabetes and advanced peripheral vascular disease, along with multiple endocrine and nonendocrine abnormalities. Genetic studies revealed a novel pathogenic variant associated with Werner syndrome. This report emphasizes the importance of precise diagnosis for prognosis and genetic counseling.
JOURNAL OF DIABETOLOGY
(2021)
Correction
Clinical Neurology
Darius Ebrahimi-Fakhari, Julian Teinert, Robert Behne, Miriam Wimmer, Angelica D'Amore, Kathrin Eberhardt, Barbara Brechmann, Marvin Ziegler, Dana M. Jensen, Premsai Nagabhyrava, Gregory Geisel, Erin Carmody, Uzma Shamshad, Kira A. Dies, Christopher J. Yuskaitis, Catherine L. Salussolia, Daniel Ebrahimi-Fakhari, Toni S. Pearson, Afshin Saffari, Andreas Ziegler, Stefan Koller, Jens Volkmann, Antje Wiesener, David R. Bearden, Shenela Lakhani, Devorah Segal, Anaita Udwadia-Hegde, Andrea Martinuzzi, Jennifer Hirst, Seth Perlman, Yoshihisa Takiyama, Georgia Xiromerisiou, Katharina Vill, William O. Walker, Anju Shukla, Rachana Dubey Gupta, Niklas Dahl, Ayse Aksoy, Helene Verhelst, Mauricio R. Delgado, Radka Kremlikova Pourova, Abdelrahim A. Sadek, Nour M. Elkhateeb, Lubov Blumkin, Alejandro J. Brea-Fernandez, David Dacruz-Alvarez, Thomas Smol, Jamal Ghoumid, Diego Miguel, Constanze Heine, Jan-Ulrich Schlump, Hendrik Langen, Jonathan Baets, Saskia Bulk, Hossein Darvish, Somayeh Bakhtiari, Michael C. Kruer, Elizabeth Lim-Melia, Nur Aydinli, Yasemin Alanay, Omnia El-Rashidy, Sheela Nampoothiri, Chirag Patel, Christian Beetz, Peter Bauer, Grace Yoon, Mireille Guillot, Steven P. Miller, Thomas Bourinaris, Henry Houlden, Laura Robelin, Mathieu Anheim, Abdullah S. Alamri, Adel A. H. Mahmoud, Soroor Inaloo, Parham Habibzadeh, Mohammad Ali Faghihi, Anna C. Jansen, Stefanie Brock, Agathe Roubertie, Basil T. Darras, Pankaj B. Agrawal, Filippo M. Santorelli, Joseph Gleeson, Maha S. Zaki, Sarah I. Sheikh, James T. Bennett, Mustafa Sahin
Article
Genetics & Heredity
Dhanya Yesodharan, Vivek Krishnan, Indu R. Nair, Aparna Ganapathy, Ashraf U. Mannan, Sheela Nampoothiri
Summary: Cenani Lenz syndrome is a rare autosomal recessive disorder caused by pathogenic variants in the LRP4 gene, leading to limb malformations and dysmorphism. The severity of the disease varies depending on the type of genetic variant.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Endocrinology & Metabolism
Brecht Guillemyn, Sheela Nampoothiri, Delfien Syx, Fransiska Malfait, Sofie Symoens
Summary: TANGO1 protein plays a crucial role in membrane recruitment and cargo secretion in the endoplasmic reticulum exit sites, with its deficiency leading to defective procollagen secretion and insufficient bone mineralization. Mutations in human TANGO1 have been associated with various diseases, including collagenopathies and skeletal abnormalities.
