Article
Endocrinology & Metabolism
Shipeng Huang, Yan Zhang, Zuan Zhan, Shuhao Gong
Summary: Laminopathies are congenital diseases caused by mutations in genes such as LMNA, LMNB, and ZMPSTE24, resulting in accelerated degeneration of human tissues. This paper presents the first case of generalized lipodystrophy-associated progeroid syndrome (GLPS) in China and compares its clinical features with existing literature. The case may provide a diagnostic and therapeutic basis for potential patients.
JOURNAL OF DIABETES INVESTIGATION
(2023)
Article
Medicine, Research & Experimental
Abhimanyu Garg, Wee-Teik Keng, Zhenkang Chen, Adwait Amod Sathe, Chao Xing, Pavithira Devi Kailasam, Yanqiu Shao, Nicholas P. Lesner, Claire B. Llamas, Anil K. Agarwal, Prashant Mishra
Summary: This study reported a rare form of progeria caused by a homozygous missense variant in the TOMM7 gene. The abnormality in mitochondrial protein import due to the mutation resulted in severe growth retardation and progeroid features.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Pediatrics
Seoyun Jang, Yo Han Ahn, Jung Min Ko, Jae Sung Ko, Sojung Lim, Hee Gyung Kang
Summary: This article reports the first pediatric case of atypical progeroid syndrome (APS) with focal segmental glomerulosclerosis (FSGS), caused by a heterozygous missense mutation in the LMNA gene. The patient presented with progeroid features, lipodystrophy, hypertrophic cardiomyopathy, and steatohepatitis. Screening for proteinuric nephropathy is essential for managing APS patients since childhood.
FRONTIERS IN PEDIATRICS
(2022)
Article
Genetics & Heredity
Bin Zuo, Hongen Xu, Zhaoyu Pan, Lu Mao, Haifeng Feng, Beiping Zeng, Wenxue Tang, Wei Lu
Summary: This study presents a case of MDPL syndrome in an 8-year-old Chinese patient, characterized by mandibular hypoplasia, characteristic facial appearance, lipodystrophy, and sensorineural hearing loss. Genetic analysis identified a de novo missense variant in the POLD1 gene, contributing to the diagnosis and clinical management of syndromic deafness.
BMC MEDICAL GENOMICS
(2022)
Article
Genetics & Heredity
Uwe Kornak, Namrata Saha, Boris Keren, Alexander Neumann, Ana Lisa Taylor Tavares, Juliette Piard, Johannes Kopp, Joao Guilherme Rodrigues Alves, Miguel Rodriguez de los Santos, Naji El Choubassi, Nadja Ehmke, Marten Jaeger, Malte Spielmann, Jean Tori Pantel, Elodie Lejeune, Beatrix Fauler, Thorsten Mielke, Jochen Hecht, David Meierhofer, Tim M. Strom, Vincent Laugel, Alexis Brice, Stefan Mundlos, Aida Bertoli-Avella, Peter Bauer, Florian Heyd, Odile Boute, Juliette Dupont, Christel Depienne, Lionel Van Maldergem, Bjoern Fischer-Zirnsak
Summary: This study successfully identified a rare progressive multisystem disease with prominent lipodystrophy and revealed the molecular genetic cause associated with the disease. The findings showed that the alternative splice product of the BUD13 gene converts a loss-of-function into a hypomorphic allele, potentially determining the severity of the disease and the survival of affected individuals.
GENETICS IN MEDICINE
(2022)
Article
Endocrinology & Metabolism
Erika Bastos Lima Freire, Mayara Ponte Madeira, Grayce Ellen da Cruz Paiva Lima, Virginia Oliveira Fernandes, Lindenberg Barbosa Aguiar, Joao Paulo Uchoa Fontenele, Ana Paula Dias Rangel Montenegro, Thyciara Fontenele Marques, Renan Galvao Ozorio, Catarina Brasil D'Alva, Renan Magalhaes Montenegro Jr
Summary: Paget's disease of bone and Congenital generalized lipodystrophy can be difficult to differentiate radiologically due to similar bone lesions but different clinical presentations. Early recognition of CGL is crucial for preventing clinical complications and premature death.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Cell Biology
Clement Crochemore, Claudia Chica, Paolo Garagnani, Giovanna Lattanzi, Steve Horvath, Alain Sarasin, Claudio Franceschi, Maria Giulia Bacalini, Miria Ricchetti
Summary: Cockayne syndrome (CS) and UV-sensitive syndrome (UVSS) are rare genetic disorders caused by mutation of the DNA repair and multifunctional CSA or CSB protein. CS displays a progeroid and neurodegenerative phenotype, and differential analysis of DNA methylation (DNAm) revealed a CS-specific epigenomic signature enriched in developmental transcription factors, ion/neurotransmitter membrane transporters and synaptic neuro-developmental genes. CS also exhibited epigenetic hallmarks of accelerated ageing, including hypomethylation of Alu sequences and increased biological age compared to healthy and UVSS cells.
Review
Endocrinology & Metabolism
David Araujo-Vilar, Antia Fernandez-Pombo, Silvia Cobelo-Gomez, Ana Castro, Sofia Sanchez-Iglesias
Summary: Lipodystrophy syndromes are rare conditions characterized by a lack of adipose tissue, leading to ectopic lipid deposition and various related disorders. These syndromes commonly affect growth, skin and appendages, adipose tissue, muscle, and bone, and can also reduce life expectancy. The molecular basis of these disorders is not well understood yet, but genomic instability, impairment of nuclear organization, chromatin structure, DNA repair, epigenetic dysregulation, and mitochondrial dysfunction are frequently observed.
HORMONES-INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM
(2022)
Article
Endocrinology & Metabolism
Takayoshi Sasako, Hiroko Kadowaki, Takayuki Fujiwara, Satoshi Kodera, Issei Komuro, Takashi Kadowaki, Toshimasa Yamauchi
Summary: This study reports a case of a Japanese woman with lipodystrophy-associated progeroid syndrome who developed severe aortic stenosis after long-term leptin replacement therapy. The patient's hypoadiponectinemia and LMNA variant may have made her susceptible to progeria-associated disorders such as aortic stenosis, which could have been exacerbated by the prolonged imbalance of adipokines caused by leptin replacement therapy.
JOURNAL OF DIABETES INVESTIGATION
(2022)
Review
Peripheral Vascular Disease
Hisaya Kato, Yoshiro Maezawa
Summary: HGPS and WS are representative genetic progeroid syndromes that have been extensively studied in the field of aging research. HGPS primarily affects children, while WS exhibits accelerated aging phenotypes after puberty. Studying these diseases can provide insight into the aging-associated development of CVD and explore potential treatment options.
JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS
(2022)
Article
Genetics & Heredity
Pui Tak Yu, Ho-Ming Luk, Myth T. Mok, F. M. Ivan Lo
Summary: Mandibular hypoplasia, deafness, progeroid feature, and lipodystrophy syndrome (MDPL) is a rare condition characterized by features such as lipodystrophy, dysmorphic features, and early onset hearing loss. This case report highlights the evolving manifestations of MDPL from childhood to adulthood in a 31-year-old Chinese woman with a specific pathogenic variant in the POLD1 gene.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Alexander Lenz, Malte Warncke, Felicia Wright, Julius Matthias Weinrich, Bjoern P. Schoennagel, Frank Oliver Henes, Gerhard Adam, Yskert von Kodolitsch, Gerhard Schoen, Peter Bannas
Summary: This study aimed to compare the growth rates of the distal aorta in Marfan patients with and without aortic root replacement. The study found that Marfan patients who underwent aortic root replacement had a higher growth rate in the distal thoracic aorta compared to those without replacement.
EUROPEAN RADIOLOGY
(2023)
Article
Multidisciplinary Sciences
Natalia Bitar da Cunha Olegario, Joel Sotero da Cunha Neto, Paulo Cirillo Souza Barbosa, Placido Rogerio Pinheiro, Pedro Lino Azevedo Landim, Ana Paula Dias Rangel Montenegro, Virginia Oliveira Fernandes, Victor Hugo Costa de Albuquerque, Joao Batista Furlan Duarte, Grayce Ellen da Cruz Paiva Lima, Renan Magalhaes Montenegro Junior
Summary: Congenital Generalized Lipodystrophy (CGL) is a rare genetic disease characterized by the absence of functional adipose tissue. Diagnosis of CGL can be based on clinical data and image processing using deep learning algorithms can be used to identify CGL phenotype.
SCIENTIFIC REPORTS
(2023)
Article
Endocrinology & Metabolism
Sara Costa, Lurdes Sampaio, Ana Berta Sousa, Chao Xing, Anil K. Agarwal, Abhimanyu Garg
Summary: This is a case report of a patient with CGL1 who showed sparing of facial fat and precocious pubertal development. The patient also had nonclassical congenital adrenal hyperplasia and responded well to hydrocortisone replacement therapy. The patient's diabetes and hypertriglyceridemia improved with metreleptin therapy, but menstrual irregularity and severe hirsutism did not.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Cardiac & Cardiovascular Systems
Shao-Wei Chen, Chia-Pin Lin, Yi-Hsin Chan, Victor Chien-Chia Wu, Yu-Ting Cheng, Ying-Chang Tung, Fu-Chih Hsiao, Dong-Yi Chen, Kuo-Chun Hung, An-Hsun Chou, Pao-Hsien Chu
Summary: This study investigated the association between fluoroquinolone use and the risk of aortic aneurysm or aortic dissection in high-risk patients with congenital aortic disease. The findings suggest that fluoroquinolone use is not associated with an increased risk of AA/AD in these patients. Further evidence is needed to establish a pharmacovigilance plan for fluoroquinolone use in this population.
CIRCULATION JOURNAL
(2023)
Article
Clinical Neurology
Yuka Murofushi, Itaru Hayakawa, Yuichi Abe, Tatsuyuki Ohto, Kei Murayama, Hisato Suzuki, Toshiki Takenouchi, Kenjiro Kosaki, Masaya Kubota
Summary: Mutations in KARS can lead to impaired protein synthesis, resulting in progressive leukodystrophies with mitochondrial dysfunction. Current therapy is limited to supportive care, but a ketogenic diet and vitamin supplementation may help alleviate symptoms and improve some functions in patients.
Letter
Genetics & Heredity
Eri Ogawa, Yuri Sakaguchi, Mikako Enokizono, Hiroshi Yoshihashi, Mamiko Yamada, Hisato Suzuki, Kenjiro Kosaki, Sahoko Miyama, Toshiki Takenouchi
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Genetics & Heredity
Yurie Ogura, Tomoko Uehara, Kota Ujibe, Hiroshi Yoshihashi, Mamiko Yamada, Hisato Suzuki, Toshiki Takenouchi, Kenjiro Kosaki, Hiromi Hirata
Summary: Mutations in the NFIA gene lead to NFIA-related disorder, characterized by developmental delay, heart defects, and distinct facial features. Zebrafish models were used to demonstrate the neurotoxicity of this gene mutation and confirm the functional impairment caused by the specific mutation in the NFIA protein.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Genetics & Heredity
Eriko Nishi, Toshiki Takenouchi, Fuyuki Miya, Tomoko Uehara, Kumiko Yanagi, Yuiko Hasegawa, Kimiko Ueda, Seiji Mizuno, Tadashi Kaname, Kenjiro Kosaki, Nobuhiko Okamoto
Summary: MKHK1 is a congenital disorder caused by CREBBP gene variants, characterized by psychomotor delay, intellectual disability, and autistic behavior. This study revealed that pathogenic variants in the last exon of CREBBP contribute to the development of MKHK1.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Pediatrics
Hisato Suzuki, Masatoshi Nozaki, Hiroshi Yoshihashi, Kazuo Imagawa, Daigo Kajikawa, Mamiko Yamada, Yu Yamaguchi, Naoya Morisada, Mayuko Eguchi, Shoko Ohashi, Shinsuke Ninomiya, Toshiyuki Seto, Tomoharu Tokutomi, Mariko Hida, Katsuaki Toyoshima, Masatoshi Kondo, Ayano Inui, Kenji Kurosawa, Rika Kosaki, Yushi Ito, Nobuhiko Okamoto, Kenjiro Kosaki, Toshiki Takenouchi
Summary: This study aimed to evaluate the diagnostic efficacy of medical exome, whole exome, and whole genome sequencing in different symptoms and the contribution of small copy number variations, as well as their impact on clinical management. The results showed that genome analysis had a high diagnostic yield for metabolic, renal, and neurologic phenotypes in critically ill neonates and infants. Small copy number variations detected using whole genome sequencing contributed to the overall molecular diagnosis in 5% of all patients. The resulting molecular diagnoses had a significant impact on clinical management.
JOURNAL OF PEDIATRICS
(2022)
Article
Multidisciplinary Sciences
Kodai Abe, Yasuaki Kabe, Susumu Uchiyama, Yuka W. Iwasaki, Hirotsugu Ishizu, Yoshifumi Uwamino, Toshiki Takenouchi, Shunsuke Uno, Makoto Ishii, Takahiro Maruno, Masanori Noda, Mitsuru Murata, Naoki Hasegawa, Hideyuki Saya, Yuko Kitagawa, Koichi Fukunaga, Masayuki Amagai, Haruhiko Siomi, Makoto Suematsu, Kenjiro Kosaki
Summary: Recent clinical trial showed 3CL(pro) inhibitor significantly reduces risk of hospitalization/death, while SARS-CoV-2 sub-lineage with reduced 3CL(pro) enzymatic activity exhibits milder clinical course. Structural perturbation surrounding substrate-binding region of mutant 3CL(pro) may explain the decreased activity.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Hisato Suzuki, Simo Li, Tomoharu Tokutomi, Chisen Takeuchi, Miyuki Takahashi, Mamiko Yamada, Hironobu Okuno, Fuyuki Miya, Toshiki Takenouchi, Hironao Numabe, Kenjiro Kosaki, Toshio Ohshima
Summary: In this study, two patients with CRMP2 non-synonymous variants were described, showing intellectual disability and hypoplasia of the corpus callosum. Functional assays using zebrafish and cellular experiments demonstrated that these variants resulted in the loss-of-function of CRMP2 protein, supporting the idea that pathogenic variants in CRMP2 can cause intellectual disabilities in humans.
HUMAN MOLECULAR GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Hisato Suzuki, Kana Aoki, Kenji Kurosawa, Kazuo Imagawa, Tatsuyuki Ohto, Mamiko Yamada, Toshiki Takenouchi, Kenjiro Kosaki, Tohru Ishitani
Summary: CTR9 gene mutations are associated with macrocephaly, motor delay, and intellectual disability. The mutant proteins showed stronger affinity to PAF1 protein, and knockout of ctr9 gene in zebrafish resulted in motor defects and enlargement of the telencephalon. Rescue experiments failed to restore normal function, and overexpression of human CTR9 mutant mRNA caused enlargement of telencephalon in zebrafish larvae.
HUMAN MOLECULAR GENETICS
(2022)
Letter
Genetics & Heredity
Yukiko Kuroda, Tatsuro Kumaki, Yoko Saito, Yumi Enomoto, Hisato Suzuki, Toshiki Takenouchi, Kenjiro Kosaki, Kenji Kurosawa
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Biochemistry & Molecular Biology
Takahiro Hayashi, Naoko Yano, Kengo Kora, Atsushi Yokoyama, Kanako Maizuru, Taisei Kayaki, Kinuko Nishikawa, Mitsujiro Osawa, Akira Niwa, Toshiki Takenouchi, Atsushi Hijikata, Tsuyoshi Shirai, Hisato Suzuki, Kenjiro Kosaki, Megumu K. Saito, Junko Takita, Takeshi Yoshida
Summary: Membrane fusion is mediated by SNARE proteins, and mutations in the NSF gene have been found to be associated with DEE. This study identified the pathomechanism underlying NSF-related DEE and proposed a potential therapeutic approach targeting the mTOR pathway.
HUMAN MOLECULAR GENETICS
(2023)
Article
Clinical Neurology
Shogo Ouchi, Kazuhiro Ishii, Kenjiro Kosaki, Hisato Suzuki, Mamiko Yamada, Toshiki Takenouchi, Akira Tamaoka
Summary: A patient developed cerebellar symptoms and progressive sensory and motor neuropathy, similar to Charcot-Marie-Tooth disease, followed by parkinsonism. Exome analysis revealed a COA7 gene mutation, which may be the cause of Parkinson's disease in this patient.
Article
Genetics & Heredity
Eri Ogawa, Takako Hishiki, Noriyo Hayakawa, Hisato Suzuki, Kenjiro Kosaki, Makoto Suematsu, Toshiki Takenouchi
Summary: The pyruvate dehydrogenase complex is a key link between cytosolic glycolysis and the tricarboxylic acid cycle. Treatment with vitamin B1 supplementation and a ketogenic diet resolved the symptoms of pyruvate dehydrogenase complex deficiency in an infant, including renal tubular dysfunction, central apnea, and transfusion-dependent anemia. Metabolomic analysis revealed improved mitochondrial energetics and potential biomarkers for neuronal recovery.
MOLECULAR GENETICS AND METABOLISM REPORTS
(2023)
Letter
Clinical Neurology
Yuka Murofushi, Itaru Hayakawa, Michiko Kawai, Yuichi Abe, Rika Kosaki, Hisato Suzuki, Toshiki Takenouchi, Masaya Kubota
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Clinical Neurology
Takuya Masuda, Hitoshi Osaka, Naomi Tsuchida, Satoko Miyatake, Kou Nishimura, Toshiki Takenouchi, Takao Takahashi, Naomichi Matsumoto, Takanori Yamagata
Summary: This study reported a female patient with drug-resistant epilepsy who had CNVs associated with 2q24.3 duplication, but unrelated to pyridoxine-dependent epilepsy. She did not have recurrent seizures after infancy and was able to discontinue medication.
EPILEPSY & BEHAVIOR REPORTS
(2022)
Article
Genetics & Heredity
Keisuke Watanabe, Atsuko Noguchi, Ikuko Takahashi, Mamiko Yamada, Hisato Suzuki, Toshiki Takenouchi, Kenjiro Kosaki, Tsutomu Takahashi
Summary: We report on a Japanese patient with Simpson-Golabi-Behmel syndrome, who had a de novo 240-kb deletion that included a part of GPC3. The patient exhibited macrosomia, coarse face, macrocephaly, supernumerary nipples, and cryptorchidism both prenatally and postnatally. Notably, the patient also presented with precocious puberty, with a pubertal age equivalent to 15 years at the chronological age of 11.5 years.
HUMAN GENOME VARIATION
(2022)