Article
Pediatrics
Qinlong Zeng, Yingsong Yang, Jiahong Luo, Jinmei Xu, Choufen Deng, Yuanjuan Yang, Shuming Tan, Shuxiang Sun, Yuping Li, Tong Ou
Summary: A real-time PCR-based multicolor melting curve analysis (MMCA) method was developed in this study to detect common mutations related to citrin deficiency, showing accurate and reliable results. Analysis of 5,332 newborns in southern China identified a carrier rate of 2% for SLC25A13 mutations.
FRONTIERS IN PEDIATRICS
(2021)
Article
Genetics & Heredity
Nimrod Sachs, Oded Wechsberg, Yuval E. Landau, Irit Krause, Ifat Israel Elgali, Malak Darawshe, Noam Shomron, Gabriel Lidzbarsky, Naama Orenstein
Summary: Citrin deficiency is an autosomal recessive disorder caused by pathogenic variants in the SLC25A13 gene. It presents in neonates as failure to thrive and acute liver insufficiency. A case of Citrin deficiency in a 4-week-old infant was diagnosed through comprehensive biochemical and molecular analysis, revealing a previously unknown damaging variant of the SLC25A13 gene.
Article
Endocrinology & Metabolism
Hui -An Chen, Rai-Hseng Hsu, Yu -Han Chen, Shu-Chang Chiang, Ni-Chung Lee, Wuh-Liang Hwu, Pao -Chin Chiu, Yin-Hsiu Chien
Summary: This study demonstrates the importance and cost-effectiveness of employing second-tier molecular testing to improve the detection rate of citrin deficiency by newborn screening.
MOLECULAR GENETICS AND METABOLISM
(2022)
Article
Medical Laboratory Technology
Jiansheng Lin, Weihua Lin, Yiming Lin, Weilin Peng, Zhenzhu Zheng
Summary: This study retrospectively analyzed the cases of Chinese infants with NICCD and identified multiple genetic mutations. The study also found comorbidity of NICCD and other inborn errors of metabolism in some patients.
CLINICA CHIMICA ACTA
(2024)
Article
Pediatrics
Wei-Xia Lin, Muhammad Rauf Yaqub, Zhan-Hui Zhang, Man Mao, Han-Shi Zeng, Feng-Ping Chen, Wei-Ming Li, Wen-Zhe Cai, Ying-Qiang Li, Zhi-Yong Tan, Wei Sheng, Zhi-Min Li, Xiao-Ling Tao, Yuan-Xia Li, Jun-Ping Zhang, Yao-Bin Han, Yan Li, Wu-Qiong Duan, Bao-Ni Ye, Ya-Rong Li, Yuan-Zong Song
Summary: This study investigated the molecular epidemiological features of citrin deficiency (CD) in Guangdong and Shaanxi provinces of China. The results showed that Guangdong exhibited a higher frequency of mutated SLC25A13 alleles compared to Shaanxi, with a higher c.852_855del allele frequency but a lower c.1751-5_1751-4ins(2684) frequency. The study provides important laboratory evidence for CD diagnosis and management in these two provinces.
TRANSLATIONAL PEDIATRICS
(2021)
Article
Endocrinology & Metabolism
Jun Kido, Johannes Haberle, Toju Tanaka, Masayoshi Nagao, Yoichi Wada, Chikahiko Numakura, Ryosuke Bo, Hiromi Nyuzuki, Sumito Dateki, Shinsuke Maruyama, Kei Murayama, Shinichiro Yoshida, Kimitoshi Nakamura
Summary: Citrin deficiency is an autosomal recessive disorder caused by mutations in the SLC25A13 gene. In neonates with the neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) form of the disease, various metabolic abnormalities can be present. By re-analyzing newborn screening results, a scoring system based on specific threshold levels of amino acids and acylcarnitines in dried blood spots can effectively detect pre-symptomatic newborns with citrin deficiency.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Medical Laboratory Technology
Yiming Lin, Weihua Lin, Run Su, Zhenzhu Zheng, Qingliu Fu, Gaoxiong Wang
Summary: This study aimed to investigate the incidence, proportion, and genetic features of hyperphenylalaninemia (HPA) in a southern Chinese population. The HPA screening results for 580,460 newborns were analyzed, and the incidence of HPA was estimated to be 1 in 10,365 newborns. Differential diagnosis of tetrahydrobiopterin deficiency (BH4D) is crucial for early detection of HPA.
CLINICA CHIMICA ACTA
(2022)
Article
Genetics & Heredity
Xiangchun Yang, Qiong Li, Fei Wang, Lulu Yan, Danyan Zhuang, Haiyan Qiu, Haibo Li, Liang Chen
Summary: This study identified the prevalence of PCD in Ningbo city through newborn screening and expanded the variant spectrum of SLC22A5. The findings demonstrate the clinical value of combining NBS program results with DNA analysis for the diagnosis of PCD.
FRONTIERS IN GENETICS
(2021)
Article
Pediatrics
Nicole S. Y. Liang, Abby Watts-Dickens, David Chitayat, Riyana Babul-Hirji, Pranesh Chakraborty, Robin Z. Hayeems
Summary: Most parents support the use of new-born screening technologies for conditions with only supportive interventions, although the degree of support is significantly lower compared to conditions with disease-specific treatments. The type of supportive care and age of onset of the condition do not significantly affect parental perceptions of risks and benefits for conditions without effective treatments. Parents are interested in expanded new-born screening for conditions with only supportive interventions in childhood, despite lower levels of perceived benefit for the child and greater anticipated anxiety from screen-positive results. These preferences suggest the need for ongoing deliberation of perceived benefits and risks, as well as improved approaches to education, consent, and support.
Article
Medical Laboratory Technology
Weihua Lin, Kunyi Wang, Zhenzhu Zheng, Yanru Chen, Caifeng Fu, Yiming Lin, Dongmei Chen
Summary: The incidence of primary carnitine deficiency (PCD) is relatively high in the Quanzhou area. Newborn screening is effective in early detection of PCD, and the identification of new SLC22A5 gene mutations broadens the mutation spectrum. Timely supplementation of L-carnitine can help prevent sudden death in PCD patients.
CLINICA CHIMICA ACTA
(2021)
Article
Genetics & Heredity
Yiming Lin, Weifeng Zhang, Chenggang Huang, Chunmei Lin, Weihua Lin, Weilin Peng, Qingliu Fu, Dongmei Chen
Summary: This study revealed that 24% of PCD cases would have been missed by conventional NBS. The high-throughput iPLEX assay is a powerful tool for PCD genotyping. Adding this second-tier genetic screening to the current NBS program could increase PCD detection, but further studies are needed to optimize workflow and evaluate cost-effectiveness.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Allergy
Lisa J. Kobrynski
Summary: Newborn screening for SCID is the first IEI detected through population screening, utilizing molecular testing on newborn dried blood spots. Early diagnosis and intervention can reduce morbidity and mortality, while also potentially improving patients' quality of life. Challenges remain in developing clinical consensus on testing, interventions, and immune reconstitution practices.
CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY
(2022)
Article
Genetics & Heredity
Yiming Lin, Bangbang Lin, Yanru Chen, Zhenzhu Zheng, Qingliu Fu, Weihua Lin, Weifeng Zhang
Summary: This study conducted NBS for over 500,000 newborns, revealing a PCD incidence rate of 1:11,189 in the Quanzhou area. 49 patients were diagnosed with PCD, all carrying biallelic pathogenic variants of the SLC22A5 gene. Patients with null variants were associated with low C0 levels.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Genetics & Heredity
Siyu Chang, Yi Yang, Feng Xu, Wenjun Ji, Xia Zhan, Xiaolan Gao, Ting Chen, Wenjuan Qiu, Huiwen Zhang, Lili Liang, Deyun Lu, Kaichuang Zhang, Xuefan Gu, Lianshu Han
Summary: This study analyzed the biochemical, clinical, and genetic characteristics of primary carnitine deficiency (PCD) patients identified through newborn screening in Shanghai. The results showed that mutations in the SLC22A5 gene were the main cause of PCD, and 8 novel mutations were identified. The combination of tandem mass spectrometry (MS/MS) and genetic testing improved the early diagnosis accuracy of PCD.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Sevcan Tug Bozdogan, Cem Mujde, Ibrahim Boga, Ozge Sonmezler, Abdullah Hanta, Cagla Rencuzogullari, Dilek Ozcan, Derya Ufuk Altintas, Atil Bisgin
Summary: This study evaluates the genetic testing results of 1595 newborns in Turkey with positive CF NBS program results, showing that 35.1% of patients carried at least one CF-related variant. The most common findings included compound heterozygosity for two mutations and the identification of novel variants. The study highlights the impact of NBS on genetic diagnosis centers and the diversity of CFTR mutations in the Turkish population.
Article
Clinical Neurology
Sota Iwafuchi, Atsuo Kikuchi, Wakaba Endo, Takehiko Inui, Yu Aihara, Kazuhito Satou, Tadashi Kaname, Shigeo Kure
Summary: A case study of a 21-month-old girl with ASD revealed a de novo CUL3 variant that may be related to developmental regression in some ASD patients. The study highlights the importance of screening for CUL3 variants in ASD patients, particularly those with Rett-like developmental regression.
BRAIN & DEVELOPMENT
(2021)
Article
Clinical Neurology
Tatsuro Izumi, Yu Aihara, Atsuo Kikuchi, Shigeo Kure
Summary: Two brothers with an IQSEC2 pathogenic variant exhibit early onset intellectual disability, intractable epileptic seizures, and other symptoms. The pathogenic variant was not found in other family members, suggesting the possibility of maternal gonadal mosaicism.
BRAIN & DEVELOPMENT
(2021)
Article
Multidisciplinary Sciences
Jun Takayama, Shu Tadaka, Kenji Yano, Fumiki Katsuoka, Chinatsu Gocho, Takamitsu Funayama, Satoshi Makino, Yasunobu Okamura, Atsuo Kikuchi, Sachiyo Sugimoto, Junko Kawashima, Akihito Otsuki, Jun Yasuda, Shigeo Kure, Kengo Kinoshita, Masayuki Yamamoto, Gen Tamiya
Summary: The authors assembled three Japanese genomes to create a population-specific reference genome, and demonstrated improved variant calling from exome sequencing using this reference genome.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Ryosuke Tashiro, Kuniyasu Niizuma, Jun Kasamatsu, Yuko Okuyama, Sherif Rashad, Atsuo Kikuchi, Miki Fujimura, Shigeo Kure, Naoto Ishii, Teiji Tominaga
Summary: The study found that RNF213 plays a critical role in antigen uptake, processing, and presentation, with Rnf213-KO and Rnf213-KI mice experiments showing that RNF213 deficiency leads to decreased antigen uptake and processing capabilities, resulting in the inability to effectively activate antigen-specific T cells.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Endocrinology & Metabolism
Natsuko Arai-Ichinoi, Atsuo Kikuchi, Yoichi Wada, Osamu Sakamoto, Shigeo Kure
Summary: Citrin deficiency can manifest at different symptomatic periods from neonatal period to adulthood with diverse clinical presentations. Diagnosis is crucial before the development of severe manifestations but can be challenging, as not all patients are detected through newborn mass screening and undiagnosed patients may appear healthy in childhood. Recognizing characteristics such as food preferences and history of infantile hepatopathy may aid in diagnosing citrin deficiency in childhood, particularly in cases of severe hypoglycemia or growth failure.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Genetics & Heredity
Yu Katata, Saki Uneoka, Naoya Saijyo, Yu Aihara, Takamitsu Miyazoe, Shun Koyamaishi, Yoshitsugu Oikawa, Yuya Ito, Yu Abe, Yurika Numata-Uematsu, Jun Takayama, Atsuo Kikuchi, Gen Tamiya, Mitsugu Uematsu, Shigeo Kure
Summary: Two siblings with Congenital Myasthenic Syndromes (CMS) showed symptoms immediately after birth, including hypotonia, multiple joint contractures, and low Apgar scores. Genetic testing revealed novel variants in the ALG14 gene, with the siblings receiving treatment and showing stable clinical course at ages of 5 and 2 years, making them the longest reported survivors of a severe form of CMS with the ALG14 variant.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Clinical Neurology
Hinako Kirikae, Mitsugu Uematsu, Yurika Numata-Uematsu, Naoya Saijo, Yu Katata, Yoshitsugu Oikawa, Atsuo Kikuchi, Kumiko Yanagi, Tadashi Kaname, Kazuhiro Haginoya, Shigeo Kure
Summary: This case report describes a patient with Pitt-Hopkins syndrome (PTHS) carrying a novel missense mutation in the TCF4 gene, who presented with two types of early epileptic encephalopathy. Treatment with topiramate (TPM) led to significant improvements in seizure control, EEG abnormalities, and psychomotor development.
BRAIN & DEVELOPMENT
(2022)
Article
Clinical Neurology
Moriei Shibuya, Hisao Yaoita, Kaori Kodama, Yukimune Okubo, Wakaba Endo, Takehiko Inui, Noriko Togashi, Jun Takayama, Gen Tamiya, Atsuo Kikuchi, Shigeo Kure, Kazuhiro Haginoya
Summary: This study described a patient with early-onset spinal muscular atrophy X3 (SMAX3) carrying a novel ATP7A variant. Clinical and neuroimaging findings showed predominant involvement in the proximal motor system, expanding the phenotypic variability of SMAX3. The discovery highlights the importance of considering this disorder in the differential diagnosis of patients with a type III SMA-like phenotype.
BRAIN & DEVELOPMENT
(2022)
Article
Endocrinology & Metabolism
Yoichi Wada, Natsuko Arai-Ichinoi, Atsuo Kikuchi, Shigeo Kure
Summary: Galactose mutarotase deficiency is a genetic disorder that can lead to high blood galactose levels, which can be prevented by consuming a galactose-restricted diet. Beta-galactosidase may be effective in reducing blood galactose levels and could potentially offer a novel treatment option for patients with GALM deficiency.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Article
Clinical Neurology
Takehiko Inui, Yoichi Wada, Moriei Shibuya, Natsuko Arai-Ichinoi, Yukimune Okubo, Wakaba Endo, Toshihiko Uchida, Noriko Togashi, Etsuo Naito, Kazuhiro Haginoya
Summary: This study explores the treatment options for neonatal-onset PDHC deficiency and finds that intravenous ketogenic diet therapy can improve lactic acidosis with no apparent side effects. Both cases showed better developmental outcomes compared to previously reported cases. Further studies are needed to optimize the treatment options.
BRAIN & DEVELOPMENT
(2022)
Article
Genetics & Heredity
Tomohiro Nakano, Yoji Sasahara, Atsuo Kikuchi, Kunihiko Moriya, Hidetaka Niizuma, Tetsuya Niihori, Matsuyuki Shirota, Ryo Funayama, Keiko Nakayama, Yoko Aoki, Shigeo Kure
Summary: This study reveals the impact of POLE mutations on DNA replication and cell cycle progression, with mutant patients being highly susceptible to proteasome-dependent degradation in the nucleus, resulting in impaired DNA replication and cell cycle progression.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Genetics & Heredity
Yu Aihara, Matsuyuki Shirota, Atsuo Kikuchi, Yu Katata, Yu Abe, Tetsuya Niihori, Ryo Funayama, Keiko Nakayama, Yoko Aoki, Shigeo Kure
Summary: This case report describes a two-year-old girl with developmental delay, tremor, and ataxic gait, but no obvious dystonia. Exome sequencing identified a novel variant in the ANO3 gene, which has been associated with intellectual disability. The study suggests that specific variants in the transmembrane 4 domain of ANO3 may be a cause of childhood-onset movement disorder with intellectual disability, even in the absence of dystonia.
JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Maako Kawamura, Hidekazu Shirota, Tetsuya Niihori, Keigo Komine, Masanobu Takahashi, Shin Takahashi, Eisaku Miyauchi, Hidetaka Niizuma, Atsuo Kikuchi, Hiroshi Tada, Muneaki Shimada, Naoki Kawamorita, Masayuki Kanamori, Ikuko Sugiyama, Mari Tsubata, Hitotshi Ichikawa, Jun Yasuda, Toru Furukawa, Yoko Aoki, Chikashi Ishioka
Summary: Cancer treatment is shifting towards personalized medicine, using genetic sequencing to identify therapeutic targets. This study retrospectively analyzed comprehensive genomic profiling (CGP) tests conducted at a hospital, focusing on the identification of presumed germline pathogenic variants (PGPV). The study found that confirmatory testing was recommended for 64 patients, with 17 patients testing positive for pathogenic variants. The results provide valuable insights for the management of secondary findings in genomic analysis.
JOURNAL OF HUMAN GENETICS
(2023)
Article
Medicine, Research & Experimental
Katsumori Segawa, Atsuo Kikuchi, Tomoyasu Noji, Yuki Sugiura, Keita Hiraga, Chigure Suzuki, Kazuhiro Haginoya, Yasuko Kobayashi, Mitsuhiro Matsunaga, Yuki Ochiai, Kyoko Yamada, Takuo Nishimura, Shinya Iwasawa, Wataru Shoji, Fuminori Sugihara, Kohei Nishino, Hidetaka Kosako, Masahito Ikawa, Yasuo Uchiyama, Makoto Suematsu, Hiroshi Ishikita, Shigeo Kure, Shigekazu Nagata
Summary: The study investigates the impact of ATP11A mutation on the distribution of PtdCho and SM and its effects on cell characteristics. The results reveal the physiological importance of substrate specificity of plasma membrane flippases in maintaining proper phospholipid distribution.
JOURNAL OF CLINICAL INVESTIGATION
(2021)