Takuya Hiraide, Kenji Shimizu, Yoshinori Okumura, Sachiko Miyamoto, Mitsuko Nakashima, Tsutomu Ogata, Hirotomo Saitsu
The recent introduction of genome sequencing in genetic analysis has led to the identification of pathogenic variants located in deep introns. Recently, several new tools have emerged to predict the impact of variants on splicing. Here, we present a Japanese boy of Joubert syndrome with biallelic TCTN2 variants. Exome sequencing identified only a heterozygous maternal nonsense TCTN2 variant (NM_024809.5:c.916C >T, p.(Gln306Ter)). Subsequent genome sequencing identified a deep intronic variant (c.1033+423G>A) inherited from his father...
March 10, 2023: Journal of Human Genetics
Taku Tsukamoto, Masaki Kinoshita, Kazuhiro Yamada, Hodaka Ito, Toshikazu Yamaguchi, Yoshiaki Chinen, Shinsuke Mizutani, Takahiro Fujino, Tsutomu Kobayashi, Yuji Shimura, Johji Inazawa, Junya Kuroda
Three types of chromosomal translocations, t(4;14)(p16;q32), t(14;16)(q32;q23), and t(11;14)(q13;q32), are associated with prognosis and the decision making of therapeutic strategy for multiple myeloma (MM). In this study, we developed a new diagnostic modality of the multiplex FISH in immunophenotyped cells in suspension (Immunophenotyped-Suspension-Multiplex (ISM)-FISH). For the ISM-FISH, we first subject cells in suspension to the immunostaining by anti-CD138 antibody and, then, to the hybridization with four different FISH probes for genes of IGH, FGFR3, MAF, and CCND1 tagged by different fluorescence in suspension...
March 8, 2023: Journal of Human Genetics
Hong-Xu Tao, Yi-Xin Yang, Bing Shi, Zhong-Lin Jia
Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common polygenetic disease. Although genome-wide association studies (GWAS) identified NTN1 gene as a high-priority candidate of NSCL/P, the comprehensive genetic architecture of NTN1 weren't yet known. Thus, this study aimed to determine full-scale genetic variants of NTN1 for NSCL/P in Chinese Han people. Initially, targeted sequencing of NTN1 gene was performed on 159 NSCL/P patients to identify susceptible single nucleotide polymorphisms (SNPs) associated with NSCL/P...
March 6, 2023: Journal of Human Genetics
Tugba Akin Duman, Fatma Nihal Ozturk
Germline mutations in BRCA1 and BRCA2 genes are mainly responsible for breast and/or ovarian cancer patients. Most of the mutations in these genes are single nucleotide changes or deletions/insertions of small numbers of bases, while a minority of mutations in these genes are large genomic rearrangements (LGRs). The frequency of LGRs in the Turkish population is not clearly known. Also insufficient awareness of the importance of LGRs in breast and/or ovarian cancer development can lead to some disruptions in patient management...
March 3, 2023: Journal of Human Genetics
Tahira Batool, Saba Irshad, Muhammad Riaz, Shahid Mahmood Baig, Peter Nuernberg, Muhammad Sajid Hussain
UNLABELLED: Primary microcephaly is a rare, congenital, and genetically heterogeneous disorder in which occipitofrontal head circumference is reduced by a minimum of three standard deviations (SDs) from average because of the defect in fetal brain development. OBJECTIVE: Mapping of RBBP8 gene mutation that produce autosomal recessive primary microcephaly. Insilco RBBP8 protein models prediction and analysis. METHODS: Consanguineous Pakistani family affected with non-syndromic primary microcephaly was mapped a biallelic sequence variant (c...
March 3, 2023: Journal of Human Genetics
Ying Lin, Rui Ban, Lingya Qiao, Juan Chen, Mengyang Liu, Jiaqi Liu, Qiang Shi
Mutations in the FHL1 gene can be associated with a variety of X-linked myopathies and cardiomyopathies, among which X-linked dominant scapuloperoneal myopathy is a rare phenotype. We collected the clinical data of two unrelated Chinese patients with X-linked scapuloperoneal myopathy and analyzed their clinical, pathological, muscle imaging, and genetic features. Both patients were characterized by scapular winging, bilateral Achilles tendon contractures, and weakness in shoulder-girdle and peroneal muscles...
March 3, 2023: Journal of Human Genetics
Mohanraj Krishnan, Amanda Phipps-Green, Emily M Russell, Tanya J Major, Murray Cadzow, Lisa K Stamp, Nicola Dalbeth, Jennie Harré Hindmarsh, Muhammad Qasim, Huti Watson, Shuwei Liu, Jenna C Carlson, Ryan L Minster, Nicola L Hawley, Take Naseri, Muagututi'a Sefuiva Reupena, Ranjan Deka, Stephen T McGarvey, Tony R Merriman, Rinki Murphy, Daniel E Weeks
The fat mass and obesity associated (FTO) locus consistently associates with higher body mass index (BMI) across diverse ancestral groups. However, previous small studies of people of Polynesian ancestries have failed to replicate the association. In this study, we used Bayesian meta-analysis to test rs9939609, the most replicated FTO variant, for association with BMI with a large sample (n = 6095) of Aotearoa New Zealanders of Polynesian (Māori and Pacific) ancestry and of Samoan people living in the Independent State of Samoa and in American Samoa...
March 2, 2023: Journal of Human Genetics
Yifei Xu, Guofei Feng, Taichi Yano, Sawako Masuda, Mizuho Nagao, Shimpei Gotoh, Makoto Ikejiri, Masaki Tanabe, Kazuhiko Takeuchi
Primary ciliary dyskinesia (PCD) is a hereditary disease caused by pathogenic variants in genes associated with motile cilia. Some variants responsible for PCD are reported to be ethnic-specific or geographical-specific. To identify the responsible PCD variants of Japanese PCD patients, we performed next-generation sequencing of a panel of 32 PCD genes or whole-exome sequencing in 26 newly identified Japanese PCD families. We then combined their genetic data with those from 40 Japanese PCD families reported previously, for an overall analysis of 66 unrelated Japanese PCD families...
March 2, 2023: Journal of Human Genetics
Marija Kojic, Nour E H Abbassi, Ting-Yu Lin, Alun Jones, Emma L Wakeling, Emma Clement, Vasiliki Nakou, Matthew Singleton, Dominika Dobosz, Marios Kaliakatsos, Sebastian Glatt, Brandon J Wainwright
BACKGROUND: Neurodevelopmental disorders (NDDs) are heterogeneous, debilitating conditions that include motor and cognitive disability and social deficits. The genetic factors underlying the complex phenotype of NDDs remain to be elucidated. Accumulating evidence suggest that the Elongator complex plays a role in NDDs, given that patient-derived mutations in its ELP2, ELP3, ELP4 and ELP6 subunits have been associated with these disorders. Pathogenic variants in its largest subunit ELP1 have been previously found in familial dysautonomia and medulloblastoma, with no link to NDDs affecting primarily the central nervous system...
March 2, 2023: Journal of Human Genetics
Yaqin Liu, Hongmei Li, Shasha Meng, Yunfei Xu, Sili Ni, Yanan Sun, Weihui Zhou
Generalized pustular psoriasis (GPP) is an autoinflammatory skin disease whose pathogenesis has not yet been fully elucidated. Alpha-1-antichymotrypsin(ACT) is a protein encoded by the SERPINA3 gene and an inhibitor of cathepsin G. One study of a European sample suggested that the loss of ACT function caused by SERPINA3 mutation is implicated in GPP. However, the role of SERPINA3 in the pathogenesis of GPP in other ethnic populations is unclear. To explore this, seventy children with GPP were performed next-generation sequencing to identify rare variants in the SERPINA3 gene...
February 24, 2023: Journal of Human Genetics
Mohit Kumar Divakar, Abhinav Jain, Rahul C Bhoyar, Vigneshwar Senthivel, Bani Jolly, Mohamed Imran, Disha Sharma, Anjali Bajaj, Vishu Gupta, Vinod Scaria, Sridhar Sivasubbu
Structural variants contribute to genetic variability in human genomes and they can be presented in population-specific patterns. We aimed to understand the landscape of structural variants in the genomes of healthy Indian individuals and explore their potential implications in genetic disease conditions. For the identification of structural variants, a whole genome sequencing dataset of 1029 self-declared healthy Indian individuals from the IndiGen project was analysed. Further, these variants were evaluated for potential pathogenicity and their associations with genetic diseases...
February 22, 2023: Journal of Human Genetics
Giulia Pascolini, Federica Gaudioso, Marina Baldi, Dario Alario, Francesco Dituri, Antonio Novelli, Anwar Baban
Among genodermatoses, trichothiodystrophies (TTDs) are a rare genetically heterogeneous group of syndromic conditions, presenting with skin, hair, and nail abnormalities. An extra-cutaneous involvement (craniofacial district and neurodevelopment) can be also a part of the clinical picture. The presence of photosensitivity describes three forms of TTDs: MIM#601675 (TTD1), MIM#616390 (TTD2) and MIM#616395 (TTD3), that are caused by variants afflicting some components of the DNA Nucleotide Excision Repair (NER) complex and with more marked clinical consequences...
February 22, 2023: Journal of Human Genetics
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
Cancer treatment is increasingly evolving toward personalized medicine, which sequences numerous cancer-related genes and identifies therapeutic targets. On the other hand, patients with germline pathogenic variants (GPV) have been identified as secondary findings (SF) and oncologists have been urged to handle them. All SF disclosure considerations for patients are addressed and decided at the molecular tumor boards (MTB) in the facility. In this study, we retrospectively summarized the results of all cases in which comprehensive genomic profiling (CGP) test was conducted at our hospital, and discussed the possibility of presumed germline pathogenic variants (PGPV) at MTB...
February 20, 2023: Journal of Human Genetics
Yixuan Zhong, Yiyi Wu, Yunyun Yang, Yu Chen, Rutai Hui, Mei Zhang, Weili Zhang
Changes in kidney function and the progression of chronic kidney disease (CKD) are associated with the risk of cardiovascular disease (CVD) and influenced by genetic factors. However, the association between genetic variants and kidney function in patients treated with antihypertensive drugs remains uncertain. This study aimed to examine the association between 30 variants locating at the 22 genes and the risk of kidney function evaluated by the estimated glomerular filtration rate (eGFR) in 1911 patients with hypertension from a Chinese community-based longitudinal cohort (including 1220 participants with CKD and 691 without CKD at baseline)...
February 16, 2023: Journal of Human Genetics
Kumiko Yanagi, Jonathan Coker, Kaori Miyana, Seijiro Aso, Nana Kobayashi, Kazuhito Satou, Adam Richman, Suneel Indupuru, Yoichi Matsubara, Tadashi Kaname
Joubert syndrome (JBTS) is characterized by a magnetic resonance imaging appearance called 'molar tooth sign', neonatal breathing dysregulation and hypotonia, and developmental delay. Whole-exome analysis based on short-read sequencing has often contributed to the identification of causative single-nucleotide variants in patients clinically diagnosed with JBTS. However, ~10% of them are still undiagnosed even though a single possible pathogenic variant has been identified. We report a successful identification of biallelic variants using long-read whole-genome sequencing and haplotype phasing analysis in a family with two Japanese siblings having morphological brain abnormalities...
February 10, 2023: Journal of Human Genetics
Yuxiang Zhang, Na Li, Zhiyong Ji, Haowei Bai, Ningjing Ou, Ruhui Tian, Peng Li, Erlei Zhi, Yuhua Huang, Jingpeng Zhao, Yaqin Han, Jing Zhang, Yuchuan Zhou, Zheng Li, Chencheng Yao
Non-obstructive azoospermia (NOA) is characterized by the failure of sperm production due to testicular disorders and represents the most severe form of male infertility. Growing evidences have indicated that gene defects could be the potential cause of NOA via genome-wide sequencing approaches. Here, bi-allelic deleterious variants in meiosis inhibitor protein 1 (MEI1) were identified by whole-exome sequencing in four Chinese patients with NOA. Testicular pathologic analysis and immunohistochemical staining revealed that spermatogenesis is arrested at spermatocyte stage, with defective programmed DNA double-strand breaks (DSBs) homoeostasis and meiotic chromosome synapsis in patients carrying the variants...
February 10, 2023: Journal of Human Genetics
Yuka Sugawara, Hideki Kato, Masao Nagasaki, Yoko Yoshida, Madoka Fujisawa, Naoko Minegishi, Masayuki Yamamoto, Masaomi Nangaku
Atypical hemolytic uremic syndrome (aHUS) is a rare complement-mediated disease that manifests as the triad of thrombotic microangiopathy. We identified two aHUS patients with neither anti-complement factor H (CFH) antibodies nor causative variants of seven aHUS-related genes (CFH, CFI, CFB, C3, MCP, THBD, and DGKE); however, their plasma showed increased levels of hemolysis by hemolytic assay, which strongly suggests CFH-related abnormalities. Using a copy number variation (CNV) analysis of the CFH/CFHR gene cluster, we identified CFH-CFHR1 hybrid genes in these patients...
February 9, 2023: Journal of Human Genetics
Toshihiro Tanaka
No abstract text is available yet for this article.
February 9, 2023: Journal of Human Genetics
Man Jin Kim, Sheehyun Kim, Seung Won Chae, Seungbok Lee, Jihoon G Yoon, Boram Kim, Jee-Soo Lee, Jong Hee Chae, Moon-Woo Seong, Jangsup Moon
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder affecting ciliary structure and function. PCD exhibiting dynein regulatory complex subunit 1 (DRC1) exon 1-4 deletion has been reported in several Japanese PCD patients; however, no large scale studies have been performed. Here, we aimed to determine the prevalence and founder effect of this variant in the Korean population. Using an in-house copy number variation tool, we screened for DRC1 exon 1-4 deletion in 20 patients with PCD and exome data of 1435 patients in the Seoul National University Hospital repository...
February 7, 2023: Journal of Human Genetics
Xiaole Wang, Baiyang You, Fei Yin, Chen Chen, Hailan He, Fangyun Liu, Zou Pan, Xiaoyuan Ni, Nan Pang, Jing Peng
U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an indispensable pre-mRNA splicing factor in the early process of splicing. Recently, U2AF2 was reported as a novel candidate gene associated with neurodevelopmental disorders. Herein, we report a patient with a novel presumed heterozygous missense variant in the U2AF2 gene (c.603G>T), who has a similar clinical phenotype as the patient reported before, including epilepsy, intellectual disability, language delay, microcephaly, and hypoplastic corpus callosum...
February 7, 2023: Journal of Human Genetics
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