American Journal of Medical Genetics Part A最新文献_第3页

Exploring Oral Health Related Quality of Life in Rett Syndrome Using Directed Content Analysis. 利用定向内容分析探讨Rett综合征患者口腔健康相关的生活质量

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-04-29 DOI: 10.1002/ajmg.a.64104

Yvonne Yee Lok Lai, Jenny Anne Downs, Helen Margaret Leonard, Laurence James Walsh, Sobia Zafar

{"title":"Exploring Oral Health Related Quality of Life in Rett Syndrome Using Directed Content Analysis.","authors":"Yvonne Yee Lok Lai, Jenny Anne Downs, Helen Margaret Leonard, Laurence James Walsh, Sobia Zafar","doi":"10.1002/ajmg.a.64104","DOIUrl":"https://doi.org/10.1002/ajmg.a.64104","url":null,"abstract":"No validated oral health-related quality of life (OHRQOL) instrument currently exists for those with severe intellectual and developmental disabilities and who communicate non-verbally. This qualitative study aimed to explore the domains that were important to the oral health-related quality of life in individuals with Rett syndrome (RTT). In 2021, following purposive sampling, recorded interviews were conducted with parents of individuals with a confirmed MECP2 mutation in the Australian RTT database (n = 31). Interview questions covered experiences of oral problems, the impacts of their daughter's oral health on other aspects of her life and on the lives of others, and on the family's quality of life. Directed content analysis was conducted. Seven domains were identified around the impacts of oral health on the child- discomfort, pain, eating, activities of daily living, emotional well-being, social well-being, and provision of services- affecting impacts on the patient. Five domains related to impacts on the family- emotions, activities, family function, conflict, and morale and self-efficacy to facilitate oral healthcare. The findings of this study pave the way for developing targeted OHRQOL measures for patients with RTT to understand and measure oral health impacts.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64104"},"PeriodicalIF":1.7,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dual Diagnosis of Sifrim-Hitz-Weiss Syndrome and Neurofibromatosis Type 1: Expanding the Phenotype of Cardiac Features in Sifrim-Hitz-Weiss Syndrome and Quick Literature Review. Sifrim-Hitz-Weiss综合征和1型神经纤维瘤病的双重诊断：扩大Sifrim-Hitz-Weiss综合征心脏特征的表型及快速文献综述

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-04-29 DOI: 10.1002/ajmg.a.64099

Ali Babazade, Tarik Duzenli, Serdar Mermer, Gulsum Kayhan

{"title":"Dual Diagnosis of Sifrim-Hitz-Weiss Syndrome and Neurofibromatosis Type 1: Expanding the Phenotype of Cardiac Features in Sifrim-Hitz-Weiss Syndrome and Quick Literature Review.","authors":"Ali Babazade, Tarik Duzenli, Serdar Mermer, Gulsum Kayhan","doi":"10.1002/ajmg.a.64099","DOIUrl":"https://doi.org/10.1002/ajmg.a.64099","url":null,"abstract":"Sifrim-Hitz-Weiss syndrome (SIHIWES) is a rare autosomal dominant disorder characterized by neurodevelopmental delay and variable congenital defects, including cardiac and skeletal, caused by mutations in the CHD4 gene. Neurofibromatosis type 1 (NF1) is a well-known disease characterized by cafe-au-lait spots and fibromatous tumors of the skin caused by heterozygous mutations in the NF1 gene. We report a male patient, 6 months old at the time of the first examination and 4.5 years old at the time of the second examination, with dysmorphic facial features, multiple café-au-lait spots, bilateral postaxial polydactyly, hydrocephalus, and dextrocardia. Whole exome sequencing revealed a de novo heterozygous c.4256G>A (p.Arg1419His) variant in the CHD4 and a heterozygous c.1411A>T (p.Lys471Ter) variant in the NF1 gene, compatible with the dual diagnosis of NF1 and SIHIWES. Although congenital heart anomalies have been reported as a component of SIHIWES, dextrocardia is a novel finding that has not previously been reported in this syndrome. Adding dextrocardia to the previously described findings, including polydactyly and hydrocephalus, suggests that a gene related to ciliary function may be a downstream target of CHD4.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64099"},"PeriodicalIF":1.7,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Two New Cases Expand the Phenotypic Spectrum of TUBG1 Missense Variants. 两例新病例扩展了TUBG1错义变异的表型谱。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-04-29 DOI: 10.1002/ajmg.a.64095

Roser Urreizti, Jessica Vissicchio, Mohamed Idries, Monica Cozar, Raquel Rabionet, Tyhiesia Donald, Elizabeth J Bhoj, Tomoki T Nomakuchi, Shannon C Shipley, Andrew E Timms, Ghayda M Mirzaa, Mercedes Serrano, Andrew K Sobering

引用次数: 0

Phenotypic Characterization of Seven Pediatric Patients Diagnosed With KAT6B-Related Disorders: Case Series and Review of the Literature. 7例诊断为kat6b相关疾病的儿科患者的表型特征：病例系列和文献回顾

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-04-25 DOI: 10.1002/ajmg.a.64100

Vittorio Maglione, Antonio Pizzuti, Gioia Mastromoro, Eleonora Cresta, Paola Favata, Maria Cristina Digilio, Rossella Capolino, Maria Lisa Dentici, Lorenzo Sinibaldi, Antonio Novelli, Marco Tartaglia, Gianluca Terrin, Viviana Cardilli

{"title":"Phenotypic Characterization of Seven Pediatric Patients Diagnosed With KAT6B-Related Disorders: Case Series and Review of the Literature.","authors":"Vittorio Maglione, Antonio Pizzuti, Gioia Mastromoro, Eleonora Cresta, Paola Favata, Maria Cristina Digilio, Rossella Capolino, Maria Lisa Dentici, Lorenzo Sinibaldi, Antonio Novelli, Marco Tartaglia, Gianluca Terrin, Viviana Cardilli","doi":"10.1002/ajmg.a.64100","DOIUrl":"https://doi.org/10.1002/ajmg.a.64100","url":null,"abstract":"Genitopatellar syndrome (GPS) and Say-Barber-Biesecker-Young-Simpson Syndrome (SBBYSS) are clinically distinct neurodevelopmental disorders caused by monoallelic pathogenic variants in KAT6B. In some cases, GPS and SBBYSS features can overlap, determining an intermediate phenotype. In the present study, we describe seven patients, four with a clinical diagnosis of SBBYSS and three presenting with an intermediate phenotype. All patients carried de novo pathogenic variants in KAT6B that were identified by exome sequencing. Five variants were novel. We provide both molecular and clinical findings, highlighting the previously undescribed association with two additional features: partial penoscrotal transposition and hypopigmented macules. We performed a review of the literature, listing the clinical features of 152 patients described in 33 papers, with a molecularly confirmed diagnosis of KAT6B-related disorders, reporting the frequency of each clinical feature detected in patients diagnosed with SBBYSS and GPS. The present work provides new insights into the phenotype associated with \"KAT6B-related disorders\", expanding the spectrum of features that can lead to a clinical suspicion of these conditions, also guiding the molecular investigations.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64100"},"PeriodicalIF":1.7,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prenatal Brain Abnormalities in Sodium-Dependent Multivitamin Transporter Deficiency. 钠依赖性多种维生素转运蛋白缺乏症的产前脑异常。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-04-24 DOI: 10.1002/ajmg.a.64102

Eri Ogawa, Kenjiro Kosaki, Toshiki Takenouchi

{"title":"Prenatal Brain Abnormalities in Sodium-Dependent Multivitamin Transporter Deficiency.","authors":"Eri Ogawa, Kenjiro Kosaki, Toshiki Takenouchi","doi":"10.1002/ajmg.a.64102","DOIUrl":"https://doi.org/10.1002/ajmg.a.64102","url":null,"abstract":"In treatable neurometabolic disorders, early diagnosis and prompt initiation of treatment are key to improved survival and outcomes. Biallelic variants in SLC5A6 cause sodium-dependent multivitamin transporter deficiency (OMIM # 618973), which is treatable with high-dose pantothenic acid, biotin, and alpha lipoic acid. So far, the onset has been postnatal in all reported patients. A review of the prenatal imaging showed ventriculomegaly at 32 weeks of gestation. After birth, the infant exhibited developmental regression. At 6 months of age, he developed acute metabolic shock in the setting of a urinary tract infection. Rapid exome analysis identified compound heterozygous pathogenic variants in SLC5A6 and confirmed the diagnosis of sodium-dependent multivitamin transporter deficiency. After the infant was initiated on treatment with high-dose biotin and pantothenic acid, we noted dramatic improvements in the hematological, cutaneous, cardiac, and gastrointestinal symptoms. Although the infant showed no further regression, he continued to have significant psychomotor disability. A review of the findings during pregnancy showed that the infant already had enlarged ventricles in late pregnancy, and neuroimaging on day 12 of birth showed signs of energy failure in late pregnancy. Our review of previously reported patients suggested no clear genotype-phenotype correlations, but there was little intrafamilial variability in disease onset. The present observation, for the first time, provides clinical evidence of a fetal onset in sodium-dependent multivitamin transporter deficiency. The high risk of recurrence and the low intrafamilial variability in disease onset suggest that identification and prenatal treatment in the high-risk group may be of significance.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64102"},"PeriodicalIF":1.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical and Radiological Characterization of TEFM-Associated Neurological Disorder. tefm相关神经系统疾病的临床和放射学特征。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-04-24 DOI: 10.1002/ajmg.a.64101

Naik Adarsha, Haseena Sait, Deepak Ravichandran

{"title":"Clinical and Radiological Characterization of TEFM-Associated Neurological Disorder.","authors":"Naik Adarsha, Haseena Sait, Deepak Ravichandran","doi":"10.1002/ajmg.a.64101","DOIUrl":"https://doi.org/10.1002/ajmg.a.64101","url":null,"abstract":"Transcription Elongation Factor Mitochondrial (TEFM) is a crucial component of the mitochondrial transcription machinery, playing a key role in regulating mitochondrial RNA (mtRNA) polymerase activity and ensuring efficient mitochondrial DNA transcription. Recent studies have identified pathogenic variations in the TEFM gene as the cause of a childhood-onset neurological disorder with varying severity. To date, only seven cases have been reported in the literature, all from a single study. We report the case of an adolescent male presenting with intellectual disability, behavioral abnormalities, intermittent ataxia, muscle fatigability, lateral rectus ophthalmoplegia, and generalized seizures, along with cerebellar and upper motor neuron signs, as well as unique neuroimaging findings. The intermittent nature of certain symptoms, along with muscle fatigability, resembled a neuromuscular junction (NMJ)-like disorder; however, the repetitive nerve stimulation test (RNST) was normal. Exome sequencing revealed a missense variant (c.469C>G, p.Pro157Ala), which was also observed previously in two Indian siblings. This case expands the phenotypic spectrum of TEFM-related mitochondrial disorders by presenting novel radiological findings not previously described. The identified missense variant may represent a population-specific variant and exhibits a recognizable phenotypic spectrum warranting consideration in individuals presenting with an NMJ-like disorder.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64101"},"PeriodicalIF":1.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

De Novo Splice-Site Variant in DKC1 in a Female With Clinical Features of Hoyeraal-Hreidarsson Syndrome. 具有Hoyeraal-Hreidarsson综合征临床特征的女性DKC1剪接位点突变

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-04-23 DOI: 10.1002/ajmg.a.64097

Dominique Braun, Anne Gregor, Monika Haubitz, Gabriela M Baerlocher, Cornelia Kraus, Claudine Rieubland, Christiane Zweier

{"title":"De Novo Splice-Site Variant in DKC1 in a Female With Clinical Features of Hoyeraal-Hreidarsson Syndrome.","authors":"Dominique Braun, Anne Gregor, Monika Haubitz, Gabriela M Baerlocher, Cornelia Kraus, Claudine Rieubland, Christiane Zweier","doi":"10.1002/ajmg.a.64097","DOIUrl":"https://doi.org/10.1002/ajmg.a.64097","url":null,"abstract":"The dyskerin encoding gene DKC1 plays an important role in telomerase activity and telomere maintenance. Pathogenic variants in DKC1 cause an X-linked multiorgan disease called dyskeratosis congenita (DC), the most severe form of which is Hoyeraal-Hreidarsson syndrome (HHS). HHS due to DKC1 variants has so far only been reported in hemizygous males and is associated with severe neurological impairment and progressive bone marrow failure, often causing lethality in early childhood. Heterozygous carrier females are often phenotypically normal. Here, we report a young adult female carrying a de novo splice-site variant in DKC1 and presenting with clinical features overlapping with HHS, such as intrauterine and postnatal growth retardation, microcephaly, intellectual disability, and recurrent infections, while lacking other typical aspects such as dermatological manifestations, cerebellar hypoplasia, or bone marrow failure. Aberrant splicing was confirmed with an in vitro assay, and further analysis revealed very short telomere lengths in the individual, supporting a causative role of the DKC1 variant. Our observations therefore suggest that heterozygous splice-site variants in DKC1 leading to loss of function might result in a phenotype overlapping with but not being typical for HHS in females, supporting a potential genotype-phenotype correlation.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64097"},"PeriodicalIF":1.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New Phenotypic Features in FGFR1-Related Osteoglophonic Dysplasia. fgfr1相关骨红蛋白发育不良的新表型特征

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-04-22 DOI: 10.1002/ajmg.a.64092

Amna A Othman, Holly E Babcock, Corey S Gill, Jamie L Fraser, Debra S Regier, Rajdeep Kaur, Kara L Simpson, Carlos R Ferreira

引用次数: 0

A Novel Heterozygous Likely Pathogenic JAG1 Germline Variant in an Adult With Unilateral Persistent Fetal Vasculature. 一种新的杂合子可能致病的JAG1种系变异在单侧胎儿血管持续存在的成年人中。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-04-21 DOI: 10.1002/ajmg.a.64098

Bukola A Olarewaju, Judy B Tejon, Mohammed Tiseer Abbas, Joanne F Shen, Ali Turkmani, Marissa Susan Ellingson, Wei Shen, Mayowa Azeez Osundiji

引用次数: 0

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-04-21 DOI: 10.1002/ajmg.a.64091

Emily Woods, C Jordaan, Amaka C Offiah, J Johnston, A A Cole, J A Fernandes, Diana S Johnson

{"title":"NOTCH3-Related Lateral Meningocele Syndrome Presenting as Radiological Copenhagen Syndrome.","authors":"Emily Woods, C Jordaan, Amaka C Offiah, J Johnston, A A Cole, J A Fernandes, Diana S Johnson","doi":"10.1002/ajmg.a.64091","DOIUrl":"https://doi.org/10.1002/ajmg.a.64091","url":null,"abstract":"Lateral meningocele syndrome is a rare skeletal syndrome caused by truncating variants in the final exon of the NOTCH3 gene. It is characterized by multiple lateral meningoceles that may result in neurological sequelae. A wider systemic phenotype has been demonstrated, including musculoskeletal abnormalities, feeding difficulties, structural cardiac and renal anomalies, and facial dysmorphism. We describe the clinical details of a child who was initially diagnosed with Copenhagen syndrome (progressive non-infectious anterior vertebral body fusion), based on radiological findings, in the context of kyphosis and back pain. Later, a novel de novo c.6723_6736del p.(Glu2241AspfsTer8) NOTCH3 variant was identified from the 100,000 Genomes Project, in keeping with a genetic diagnosis of lateral meningocele syndrome. Without the context of additional features that may point toward an underlying syndrome, radiological findings-when reviewed in isolation-may be suggestive of alternate diagnoses. In this case, the radiological finding of anterior vertebral fusion suggested Copenhagen syndrome, whereas the identification of dural ectasia prompted further investigation into Ehlers-Danlos syndrome subtypes. Recognition of dysmorphology prompted wider investigation by Whole Genome Sequencing. Features of lateral meningocele syndrome significantly overlap with those of connective tissue disorders including EDS, Marfan syndrome, and Loeys-Dietz syndrome. We describe the clinical features of the here-reported proband with a novel NOTCH3 variant, and compare the phenotypes of these differential diagnoses.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64091"},"PeriodicalIF":1.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0