Human Genome Variation

Abstract We present a case of suspected CDKL5 deficiency disorder (CDD) in which a novel intragenic multi-exonic duplication in the CDKL5 gene was identified using next-generation sequencing and multiple ligation-dependent probe amplification. This duplication was assumed to result in a shift of the reading frame and the introduction of a premature stop codon. This case highlights the importance of careful phenotyping and comprehensive genetic testing to detect rare structural variants in CDD patients.

Takato Akiba

Shino Shimada

Katsumi Imai

Satoru Takahashi

A case of CDKL5 deficiency disorder with a novel intragenic multi-exonic duplication

CDKL5缺陷症伴新发基因内多外显子重复病例

Abstract Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by germline variants in the APC gene, leading to the development of numerous colorectal polyps and significantly increases the risk of colorectal cancer. A diagnosis is typically made using colonoscopy, and genetic testing can assist in patient surveillance and carrier identification. Recent advances include the use of whole-genome array comparative genomic hybridization (a-CGH), which provides better resolution of genetic imbalances. We aimed to explore the specific features of FAP patients with whole APC gene deletions using high-resolution a-CGH and to compare patient characteristics. Two polyposis patients with whole APC deletions were identified, and the lost genetic sizes ranged from 0.3–1.1 Mb. Nervous abnormalities were a characteristic symptom in a patient with a 1.1 Mb loss. A patient with an approximately 0.3 Mb loss, which included the entire APC gene, presented a polyposis phenotype without intellectual disability. The comparison of genetic losses, with or without intellectual disability, revealed 7 genetic changes. Consequently, EPB41L4A is a candidate gene associated with the neurogenic phenotype.

Hiroki Tanabe

Yasuyuki Koshizuka

Kazuyuki Tanaka

Kenji Takahashi

Masami Ijiri

Keitaro Takahashi

Katsuyoshi Ando

Nobuhiro Ueno

Shin Kashima

Takeo Sarashina

Kentaro Moriichi

Kenrokuro Mitsube

Yusuke Mizukami

Mikihiro Fujiya

Yoshio Makita

High-resolution genetic analysis of whole APC gene deletions: a report of two cases and patient characteristics

高分辨率全APC基因缺失的遗传分析：两例报告及患者特征

Abstract Bryant-Li-Bhoj syndrome (BLBS; OMIM # 619720, 619721), caused by germline H3F3A and H3F3B variants encoding histone H3.3, is characterized by mild to severe developmental delay, intellectual disability, failure to thrive, muscle tone abnormalities, and dysmorphic facial features. Here, we present a Japanese patient with a novel heterozygous p.A48G variant in H3F3A , displaying previously unrecognized symptoms of neonatal myoclonus. This case helps broaden the phenotypic spectrum of BLBS.

Moemi Hojo

Noriko Soma

Kei Yamada

Yu Kobayashi

Masaki Miura

Hitomi Fujii

Hiromi Nyuzuki

Yosuke Nishio

Taichi Oso

Tomoo Ogi

Takeshi Ikeuchi

Jun Tohyama

Neonatal myoclonus in Bryant-Li-Bhoj syndrome associated with a novel H3F3A variant

Bryant-Li-Bhoj综合征中新生儿肌阵挛与新型H3F3A变异相关

Abstract Neurofibromatosis type 1 (NF1) presents with a broad spectrum of clinical manifestations, including an increased risk of tumor development and hypertension. Comprehensive data on genotype‒phenotype correlations in patients with NF1 are limited. Therefore, in this study, we aimed to elucidate the detailed genetic and clinical characteristics of NF1 in a hereditary tumor cohort. We performed sequencing and copy number assays in a clinical laboratory and analyzed the clinical data of 44 patients with suspected NF1. Germline pathogenic variants were detected in 36 patients (81.8%), and 20.7% of the variants were novel. Notably, 40.0% of adult patients presented with malignancies; female breast cancer occurred in 20.0% of patients, which was a higher rate than that previously reported. Hypertension was observed in 30.6% of the adult patients, with one patient experiencing sudden death and another developing pheochromocytoma. Three patients with large deletions in NF1 exhibited prominent cutaneous, skeletal, and neurological manifestations. These results highlight the importance of regular surveillance, particularly for patients with malignancies and hypertension. Our findings provide valuable insights for genetic counseling and clinical management, highlighting the multiple health risks associated with NF1 and the need for comprehensive and multidisciplinary care.

Mashu Futagawa

Tetsuya Okazaki

Eiji Nakata

Chika Fukano

Risa Osumi

Fumino Kato

Yusaku Urakawa

Hideki Yamamoto

Toshifumi Ozaki

Akira Hirasawa

Genotypes and phenotypes of neurofibromatosis type 1 patients in Japan: A Hereditary Tumor Cohort Study

日本神经纤维瘤病1型患者的基因型和表型：一项遗传性肿瘤队列研究

Abstract Genetic testing identified novel compound heterozygous missense variants in the HEXA gene (NM_00520.6: c.775A&gt;C and NM_000520.6: c.508C&gt;T) in a 16-month-old girl diagnosed with Tay‒Sachs disease. The patient gradually became unable to consume food orally. She suffered severe aspiration pneumonia and underwent gastrostomy and laryngotracheal separation at 2 years and 4 months of age. Despite an initially good prognosis, she died at 3 years of age.

Masaharu Moroto

Uda Daisuke

Tomoya Yodoi

Yoshihiro Nitta

Yohei Sugimoto

Tomohiro Chiyonobu

Hiroyuki Yamada

Kayo Ozaki

Taichi Nakatani

Norio Sakai

Simultaneous surgery for gastrostomy and laryngotracheal separation in a patient with Tay‒Sachs disease

Tay-Sachs病患者同时进行胃造口术和喉气管分离手术

Abstract We report a case of a fetus with short-rib thoracic dysplasia (SRTD) with polydactyly that also presented with atypical severe acro-mesomelic ossification defects. Genetic analysis using massively parallel sequencing of a skeletal dysplasia panel revealed compound heterozygous variants in DYNC2H1 . This clinical report highlights the challenges associated with diagnosing the diverse phenotypes in the SRTD group and emphasizes the importance of genetic surveillance with a targeted gene panel for accurate diagnosis.

Erika Nakajima

Yuko Yokohama

Saori Sugiyama

Mio Taketazu

Takahiro Yamada

Anna Hammarsjö

Giedre Grigelioniene

Gen Nishimura

Unclassifiable short-rib thoracic dysplasia diagnosed using targeted gene panel sequencing

使用靶向基因组测序诊断的不可分类短肋胸廓发育不良

短名	Hum. Genome Var.
Journal Impact	0.85
国际分区	GENETICS & HEREDITY(Q4)

ISSN	2054-345X
h-index	23

涉及主题	生物遗传学化学生物化学基因医学突变内科学表型心理学病理精神科等位基因错义突变儿科内分泌学
出版信息	出版商: Nature Publishing Group，出版周期: ，期刊类型: journal，开源期刊: 是
基本数据	创刊年份: 2014，原创研究文献占比: 93.48%，自引率:10.00%， Gold OA占比: 98.35%
期刊费用	$3090详情
平均审稿周期	网友分享经验：13 Weeks

Human Genome Variation

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A case of CDKL5 deficiency disorder with a novel intragenic multi-exonic duplication

High-resolution genetic analysis of whole APC gene deletions: a report of two cases and patient characteristics

Neonatal myoclonus in Bryant-Li-Bhoj syndrome associated with a novel H3F3A variant

Genotypes and phenotypes of neurofibromatosis type 1 patients in Japan: A Hereditary Tumor Cohort Study

Simultaneous surgery for gastrostomy and laryngotracheal separation in a patient with Tay‒Sachs disease

High-resolution genetic analysis of whole APC gene deletions: a report of two cases and patient characteristics

Neonatal myoclonus in Bryant-Li-Bhoj syndrome associated with a novel H3F3A variant

Unclassifiable short-rib thoracic dysplasia diagnosed using targeted gene panel sequencing

Simultaneous surgery for gastrostomy and laryngotracheal separation in a patient with Tay‒Sachs disease

Genotypes and phenotypes of neurofibromatosis type 1 patients in Japan: A Hereditary Tumor Cohort Study