Application of Clinical Genetics

Abstract: Acute intermittent porphyria (AIP) is due to a deficiency of the third enzyme, the hydroxymethylbilane synthase, in heme biosynthesis. It manifests with occasional neuropsychiatric crises associated with overproduction of porphyrin precursors, aminolevulinic acid and porphobilinogen. The clinical criteria of an acute attack include the paroxysmal nature and various combinations of symptoms, such as abdominal pain, autonomic dysfunction, hyponatremia, muscle weakness, or mental symptoms, in the absence of other obvious causes. Intensive abdominal pain without peritoneal signs, acute peripheral neuropathy, and encephalopathy usually with seizures or psychosis are the key symptoms indicating possible acute porphyria. More than fivefold elevation of urinary porphobilinogen excretion together with typical symptoms of an acute attack is sufficient to start a treatment. Currently, the prognosis of the patients with AIP is good, but physicians should be aware of a potentially fatal outcome of the disease. Mutation screening and identification of type of acute porphyria can be done at the quiescent phase of the disease. The management of patients with AIP include following strategies: A, during an acute attack: 1) treatment with heme preparations, if an acute attack is severe or moderate; 2) symptomatic treatment of autonomic dysfunctions, polyneuropathy and encephalopathy; 3) exclusion of precipitating factors; and 4) adequate nutrition and fluid therapy. B, during remission: 1) exclusion of precipitating factors (education of patients and family doctors), 2) information about on-line drug lists, and 3) mutation screening for family members and education about precipitating factors in mutation-positive family members. C, management of patients with recurrent attacks: 1) evaluation of the lifestyle, 2) evaluation of hormonal therapy in women, 3) prophylactic heme therapy, and 4) liver transplantation in patients with severe recurrent attacks. D, follow-up of the AIP patients for long-term complications: chronic hypertension, chronic kidney insufficiency, chronic pain syndrome, and hepatocellular carcinoma. Keywords: porphyria, acute intermittent porphyria, neuropathy, treatment, heme

Elena Pischik

Raili Kauppinen

The Application of Clinical Genetics

An update of clinical management of acute intermittent porphyria

急性间歇性卟啉病临床管理最新进展

Abstract: Spinal muscular atrophy (SMA) is a heritable neuromuscular disorder that causes degeneration of the alpha motor neurons from anterior horn cells in the spinal cord, which causes severe progressive hypotonia and muscular weakness. With a carrier frequency of 1 in 40– 50 and an estimated incidence of 1 in 10,000 live births, SMA is the second most common autosomal recessive disorder. Affected individuals with SMA have a homozygous loss of function of the survival motor neuron gene SMN1 on 5q13 but keep the modifying SMN2 gene. The most common mutation causing SMA is a homozygous deletion of the SMN1 exon 7, which can be readily detected and used as a sensitive diagnostic test. Because SMN2 produces a reduced number of full-length transcripts, the number of SMN2 copies can modify the clinical phenotype and as such, becomes an essential predictive factor. Population-based SMA carrier screening identifies carrier couples that may pass on this genetic disorder to their offspring and allows the carriers to make informed reproductive choices or prepare for immediate treatment for an affected child. Three treatments have recently been approved by the Food and Drug Administration (FDA). Nusinersen increases the expression levels of the SMN protein using an antisense oligonucleotide to alter splicing of the SMN2 transcript. Onasemnogene abeparvovec is a gene therapy that utilizes an adeno-associated virus serotype 9 vector to increase low functional SMN protein levels. Risdiplam is a small molecule that alters SMN2 splicing in order to increase functional SMN protein. Newborn screening for SMA has been shown to be successful in allowing infants to be treated before the loss of motor neurons and has resulted in improved clinical outcomes. Several of the recommendations and guidelines in the review are based on studies performed in the United States. Keywords: spinal muscular atrophy, carrier screening, newborn screening, SMA treatment

Melissa C Keinath

Devin E Prior

Thomas W Prior

TACG

Spinal Muscular Atrophy: Mutations, Testing, and Clinical Relevance

脊髓性肌萎缩症：突变、检测与临床意义

Oliwia Rdzanek

Patrycja Najda

Karolina Parysek-Wójcik

Anna Pytlik

Monika Lejman

Joanna Zawitkowska

Bilateral Wilms Tumor - Case Report of a Patient with Family History

双侧威尔姆氏瘤 - 有家族史患者的病例报告

The aim of this study is to analyze available research on targeting signaling pathways for the development of new drugs in patients with T-cell acute lymphoblastic leukemia (T-ALL). This analysis focuses specifically on the role of LCK tyrosine kinase and mTOR signaling pathways in pediatric patients. Outcome: Current literature suggests that these pathways play a significant role in the regulation of T-cell cycles, making them potential therapeutic targets. However, despite promising findings, there remains a need for further research, particularly in pediatric populations, to fully understand the therapeutic implications and to optimize drug development. The conclusion drawn from this analysis highlights the significant influence of LCK and mTOR on T-cell cycle regulation, underscoring the importance of continued investigation in this area.

Agata Rocka

Maria Suchcicka

Aleksandra M Jankowska

Magdalena M Woźniak

Pathway of LCK Tyrosine Kinase and mTOR Signaling in Children with T-Cell Acute Lymphoblastic Leukemia

LCK酪氨酸激酶与mTOR信号通路在儿童T细胞急性淋巴细胞白血病中的作用途径

Introduction: Syndromic hearing loss (SHL) is characterized by distinctive clinical phenotypes as well as genetic and phenotypic heterogeneity. More than 400 species of SHL have been described, the majority of which are autosomal dominant. Methods: 11 forms of SHL were obtained from 14 unrelated families with probands ranging in age from 5 to 78 months. The results of whole exome sequencing(WES), audiological characteristics, middle and inner ear radiological findings, and additional clinical phenotype characteristics were retrospectively analyzed. Results: Fourteen people with SHL were found. Two of them had Waardenburg syndrome, two had Branchio-Oto-Renal syndrome, two had CHARGE syndrome, and one had Treacher Collins syndrome, Kleefstra syndrome, Muenke syndrome, Osteopathia Striata with Cranial Sclerosis, Ayme-Gripp syndrome, Tatton-Brown-Rahman syndrome, Stickler syndrome, or Stapes Ankylosis with Broad Thumbs and Toes. In this investigation, ten variants were first reported. Discussion: The combination of a neonatal hearing screening and WES can diagnose syndrome-type hearing loss in infancy and childhood, according to our findings, expansion of the gene variant spectrum and phenotype for various age groups of SHL is essential and can provide valuable guidelines for clinical intervention decisions. It is imperative for medical practitioners to conduct diligent and prolonged patient monitoring due to the inherent variability in both the auditory impairment and the comprehensive clinical manifestation of SHL. Keywords: syndromic hearing loss, whole exome sequencing, neonatal hearing screening, phenotype-genotype correlations

Zhoushu Zheng

Lulu Yan

Lu Ding

Yinghui Zhang

Meihong Wang

Yihui Yang

Junhua Wu

Changshui Chen

Ming Tang

Haibo Li

Comparison of Genetic, Auditory Features, and Systemic Clinical Phenotype in 14 Families with Syndromic Hearing Loss

14个综合征性听力损失家系的遗传、听觉特征及系统性临床表型比较

Shuang Lv

Yiming Li

Bojian Sun

Yu Jing

Xing Wang

Zhanqing Gu

Bailiang Wang

Cheng Xiao

Association of RIPK1 and RIPK2 Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Han Population

中国汉族人群中RIPK1和RIPK2基因多态性与类风湿性关节炎的关联研究

Lamia Alshamlani

Dana Alsulaim

Raghad Alabbad

Ahad Alhoshan

Joud Alkhoder

Norah Alsaleh

Mohammed Almannai

Faroug Ababneh

Manal Algattan

Lojain Alsini

Abdulrahman Alswaid

Wafaa Eyaid

Fuad Al Mutairi

Muhammad Umair

Majid Alfadhel

Consanguinity and Occurrence of Monogenic Diseases in a Single Tertiary Centre in Riyadh, Saudi Arabia: A 2 Years Cross-Sectional Study

近亲结婚与沙特阿拉伯利雅得一家三级医院单基因疾病发生率的关联：一项为期2年的横断面研究

短名	TACG
Journal Impact	2.70
国际分区	GENETICS & HEREDITY(Q2)

ISSN	1178-704X
h-index	40

涉及主题	生物医学遗传学化学生物化学内科学基因病理心理学疾病生物信息学精神科内分泌学表型基因型突变儿科
出版信息	出版商: Dove Medical Press Ltd.，出版周期: ，期刊类型: journal，开源期刊: 是
基本数据	创刊年份: 2008，原创研究文献占比: 93.75%，自引率:0.00%， Gold OA占比: 94.29%
期刊费用	$2990详情
平均审稿周期	网友分享经验：16 Weeks

Application of Clinical Genetics

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An update of clinical management of acute intermittent porphyria

Spinal Muscular Atrophy: Mutations, Testing, and Clinical Relevance

Bilateral Wilms Tumor - Case Report of a Patient with Family History

Pathway of LCK Tyrosine Kinase and mTOR Signaling in Children with T-Cell Acute Lymphoblastic Leukemia

Comparison of Genetic, Auditory Features, and Systemic Clinical Phenotype in 14 Families with Syndromic Hearing Loss

Bilateral Wilms Tumor - Case Report of a Patient with Family History

Pathway of LCK Tyrosine Kinase and mTOR Signaling in Children with T-Cell Acute Lymphoblastic Leukemia

Comparison of Genetic, Auditory Features, and Systemic Clinical Phenotype in 14 Families with Syndromic Hearing Loss

Association of RIPK1 and RIPK2 Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Han Population

Consanguinity and Occurrence of Monogenic Diseases in a Single Tertiary Centre in Riyadh, Saudi Arabia: A 2 Years Cross-Sectional Study