Two families with TET3-related disorder showing neurodevelopmental delay with craniofacial dysmorphisms

Seyama, Rie; Tsuchida, Naomi; Okada, Y.; Sakata, Sonoko; Hamada, Keisuke; Azuma, Yoshiteru; Hamanaka, Kohei; Fujita, Atsushi; Koshimizu, Eriko; Miyatake, Satoko; Mizuguchi, Takeshi; Makino, Shintaro; Itakura, Atsuo; Okada, Satoshi; Okamoto, Nobuhiko; Ogata, Kazuhiro; Uchiyama, Yuri; Matsumoto, Naomichi

doi:10.1038/s10038-021-00986-y

Cited by 20 publications

(14 citation statements)

References 23 publications

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“…Genomic DNA was obtained from peripheral blood leukocytes of all individuals using QuickGene 610L (Wako, Osaka, Japan). We performed whole‐exome sequencing (WES) as previously described 5 . In brief, genomic DNA was captured using SureSelect Human All Exon V5 or V6 (Agilent Technologies, Santa Clara, CA) or Twist Comprehensive Exome Panel (Twist Bioscience, South San Francisco, CA), and the captured libraries were sequenced on an Illumina HiSeq 2500 with 101‐bp paired‐end reads or an Illumina NovaSeq with 151‐bp paired‐end reads (Illumina, San Diego, CA).…”

Section: Methodsmentioning

confidence: 99%

“…We performed whole-exome sequencing (WES) as previously described. 5 In brief, genomic DNA was captured using SureSelect Human All Exon V5 or V6 (Agilent Technologies, Santa Clara, CA) or Twist Comprehensive Exome Panel (Twist Bioscience, South San Francisco, CA), and the captured libraries were sequenced on an Illumina HiSeq 2500 with 101-bp paired-end reads or an Illumina NovaSeq with 151-bp paired-end reads (Illumina, San Diego, CA). Image analysis and base calling were performed using sequence control software with real-time analysis and CASAVA software (Illumina).…”

Section: Genetic Analysismentioning

confidence: 99%

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De novo heterozygous variants in KIF5B cause kyphomelic dysplasia

et al. 2022

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Kyphomelic dysplasia is a heterogeneous group of skeletal dysplasias characterized by severe bowing of the limbs associated with other variable findings, such as narrow thorax and abnormal facies. We searched for the genetic etiology of this disorder.Toshiyuki Itai, Zheng Wang, and Gen Nishimura contributed equally to this study.Naomichi Matsumoto and Shiro Ikegawa supervised equally to this study.

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Section: Methodsmentioning

confidence: 99%

Section: Genetic Analysismentioning

confidence: 99%

De novo heterozygous variants in KIF5B cause kyphomelic dysplasia

et al. 2022

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“…Genomic DNA was obtained from peripheral blood leukocytes of all individuals using QuickGene 610L (Wako, Osaka, Japan). We performed whole-exome sequencing (WES) as previously described 12 . In brief, genomic DNA was captured using SureSelect Human All Exon V5 or V6 (Agilent Technologies, Santa Clara, CA, USA), and the captured libraries were sequenced on an Illumina HiSeq 2500 with 101-bp paired-end reads.…”

Section: Methodsmentioning

confidence: 99%

A novel NONO variant that causes developmental delay and cardiac phenotypes

Itai

Sugie

Nitta

et al. 2023

Sci Rep

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The Drosophila behavior/human splicing protein family is involved in numerous steps of gene regulation. In humans, this family consists of three proteins: SFPQ, PSPC1, and NONO. Hemizygous loss-of-function (LoF) variants in NONO cause a developmental delay with several complications (e.g., distinctive facial features, cardiac symptoms, and skeletal symptoms) in an X-linked recessive manner. Most of the reported variants have been LoF variants, and two missense variants have been reported as likely deleterious but with no functional validation. We report three individuals from two families harboring an identical missense variant that is located in the nuclear localization signal, NONO: NM_001145408.2:c.1375C > G p.(Pro459Ala). All of them were male and the variant was inherited from their asymptomatic mothers. Individual 1 was diagnosed with developmental delay and cardiac phenotypes (ventricular tachycardia and dilated cardiomyopathy), which overlapped with the features of reported individuals having NONO LoF variants. Individuals 2 and 3 were monozygotic twins. Unlike in Individual 1, developmental delay with autistic features was the only symptom found in them. A fly experiment and cell localization experiment showed that the NONO variant impaired its proper intranuclear localization, leading to mild LoF. Our findings suggest that deleterious NONO missense variants should be taken into consideration when whole-exome sequencing is performed on male individuals with developmental delay with or without cardiac symptoms.

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“…Trio-whole exome sequencing was performed by our local genome diagnostic laboratory and processed according to standardised diagnostic pipelines 13 14…”

Section: Methodsmentioning

confidence: 99%

Clinical diversity and molecular mechanism of VPS35L-associated Ritscher-Schinzel syndrome

et al. 2022

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PurposeThe Retriever subunit VPS35L is the third responsible gene for Ritscher-Schinzel syndrome (RSS) after WASHC5 and CCDC22. To date, only one pair of siblings have been reported and their condition was significantly more severe than typical RSS. This study aimed to understand the clinical spectrum and underlying molecular mechanism in VPS35L-associated RSS. Methods We report three new patients with biallelic VPS35L variants. Biochemical and cellular analyses were performed to elucidate disease aetiology. Results. In addition to typical features of RSS, we confirmed hypercholesterolaemia, hypogammaglobulinaemia and intestinal lymphangiectasia as novel complications of VPS35Lassociated RSS. The latter two complications as well as proteinuria have not been reported in patients with CCDC22 and WASHC5 variants. One patient showed a severe phenotype and the other two were milder. Cells established from patients with the milder phenotypes showed relatively higher VPS35L protein expression. Cellular analysis found VPS35L ablation decreased the cell surface level of lipoprotein receptor-related protein 1 and low-density lipoprotein receptor, resulting in reduced low-density lipoprotein cellular uptake. Conclusion VPS35L-associated RSS is a distinct clinical entity with diverse phenotype and severity, with a possible molecular mechanism of hypercholesterolaemia. These findings provide new insight into the essential and distinctive role of Retriever in human development. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY⇒ This study contributes to the establishment of a disease concept for VPS35L-associated RSS, and provides new insight into the essential and distinctive role of Retriever in human development.

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Two families with TET3-related disorder showing neurodevelopmental delay with craniofacial dysmorphisms

Cited by 20 publications

References 23 publications

De novo heterozygous variants in KIF5B cause kyphomelic dysplasia

De novo heterozygous variants in KIF5B cause kyphomelic dysplasia

A novel NONO variant that causes developmental delay and cardiac phenotypes

Clinical diversity and molecular mechanism of VPS35L-associated Ritscher-Schinzel syndrome

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