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

Sleep Disturbances in Adults With Tuberous Sclerosis Complex: Influences of Treatment and Clinical Features 成人结节性硬化症患者的睡眠障碍：治疗和临床特征的影响

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2026-10-09 Epub Date: 2026-06-01 DOI: 10.1002/ajmg.a.70217

Kirstin A. Risgaard, Laura Farach, Hope Northrup, Sarah L. Wilson, Deborah Pearson, Syed Hashmi, Kate Richardson

{"title":"Sleep Disturbances in Adults With Tuberous Sclerosis Complex: Influences of Treatment and Clinical Features","authors":"Kirstin A. Risgaard, Laura Farach, Hope Northrup, Sarah L. Wilson, Deborah Pearson, Syed Hashmi, Kate Richardson","doi":"10.1002/ajmg.a.70217","DOIUrl":"10.1002/ajmg.a.70217","url":null,"abstract":"Tuberous sclerosis complex (TSC) is a genetic condition with multisystem neurocutaneous signs, including hamartomas, epilepsy, and neuropsychological difficulties. Although sleep disorders are increasingly recognized in TSC, they remain poorly described in adults. Additionally, the influence of clinical features and commonly used medications on sleep is not well understood. This study assessed sleep disorders in adults with TSC and examined contributing clinical and treatment factors. Adults were recruited through the TSC Alliance and the TSC Center of Excellence (CoE) at UTHealth Houston. Sleep quality was assessed using the Pittsburgh Sleep Quality Index, and demographic, clinical, lifestyle, and medication information was collected from 84 adults. Descriptive and inferential statistics were applied, with significance set at p < 0.05. Overall, 64% (n = 54) met criteria for poor sleep, significantly higher than rates reported in neurotypical adults (p < 0.001). Participants with mental illness or anxiety more frequently reported sleep issues (p = 0.009, p = 0.04). Poor sleep was also associated with use of mTOR inhibitors, antiepileptic drugs, and antidepressants (p\u0000 AD = 0.016, p\u0000 mTORi < 0.001, p\u0000 AEDs = 0.045). These results highlight sleep disruption as a common and clinically relevant feature of TSC and emphasize the need for providers to assess sleep carefully, considering both clinical signs and medication effects when developing management plans.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":"200 11","pages":"2454-2463"},"PeriodicalIF":1.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.a.70217","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Two Atypical Cases of Adams–Oliver Syndrome With DOCK6 Genetic Variants 伴有DOCK6基因变异的亚当斯-奥利弗综合征2例。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2026-10-09 Epub Date: 2026-05-27 DOI: 10.1002/ajmg.a.70206

Yan Bai, Jiaxin Xu, Jing Xin, Wenhui Mo, Mingwei Huang, Chunzhi Tang

引用次数: 0

PUS7 Deficiency: Phenotypical Expansion of PUS7-Related Neurodevelopmental Disorders PUS7缺乏：PUS7相关神经发育障碍的表型扩展。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2026-10-09 Epub Date: 2026-06-01 DOI: 10.1002/ajmg.a.70220

Alice Muda, Barbara Belmessieri, Patrizia Accorsi, Jessica Galli, Edoardo Errichiello, Lucio Giordano

{"title":"PUS7 Deficiency: Phenotypical Expansion of PUS7-Related Neurodevelopmental Disorders","authors":"Alice Muda, Barbara Belmessieri, Patrizia Accorsi, Jessica Galli, Edoardo Errichiello, Lucio Giordano","doi":"10.1002/ajmg.a.70220","DOIUrl":"10.1002/ajmg.a.70220","url":null,"abstract":"Pathogenic variants in PUS7, encoding pseudouridine synthase 7, cause a rare neurodevelopmental disorder marked by intellectual disability, microcephaly, short stature, and behavioral disturbances. Since the first report in 2018, only 16 patients have been described. We report a novel case with a homozygous pathogenic PUS7 variant and present an updated review of all cases published between 2018 and 2025. Across 17 cases, the most frequent features were moderate/severe intellectual disability, delayed/absent speech, aggressive behavior, microcephaly, mild facial dysmorphisms, motor delay, and short stature. These features are common but non-specific, with the exception of aggressiveness that manifests at a very early age. Less common but more peculiar findings included sensorineural hearing loss, autistic traits, self-injurious behavior, and motor stereotypies. The combination of core features with these more specific symptoms should prompt suspicion of a PUS7-related disorder. We recommend looking for PUS7 pathological variants when performing whole exome sequencing in children with this constellation of neurodevelopmental and behavioral signs.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":"200 11","pages":"2547-2552"},"PeriodicalIF":1.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.a.70220","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Table of Contents, Volume 200A, Number 11, November 2026 目录，200A卷，第11号，2026年11月

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2026-10-09 DOI: 10.1002/ajmg.a.70310

引用次数: 0

Syndrome of the Month: Van den Ende-Gupta Syndrome 本月综合征：Van den Ende-Gupta综合征：格式塔诊断，结果和建议。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2026-10-09 Epub Date: 2026-06-03 DOI: 10.1002/ajmg.a.70190

Shubha Phadke

{"title":"Syndrome of the Month: Van den Ende-Gupta Syndrome","authors":"Shubha Phadke","doi":"10.1002/ajmg.a.70190","DOIUrl":"10.1002/ajmg.a.70190","url":null,"abstract":"<div>\u0000 \u0000 Van den Ende-Gupta syndrome (VDEGS) is an autosomal recessive disorder involving self-resolving joint contractures that are present since birth. Because of characteristic facial features, clinical diagnosis may be suspected by experienced clinicians or identified using facial recognition-based software. Confirmation by identification of disease-causing biallelic variants in SCARF2 can be helpful to definitively provide a clinico-molecular diagnosis to differentiate VDEGS from other disorders with overlapping phenotypes with blepharophimosis, arachnodactyly, and camptodactyly. Most affected individuals do not have major malformations or intellectual disability. However, occasional patients with ophthalmological, genitourinary, or laryngeal abnormalities are reported, indicating the need for a detailed evaluation. The causative gene, SCARF2, is located within the region of the 22q11.2 microdeletion syndrome. Two cases with microdeletion of the region on one chromosome and a SCARF2 variant on the other chromosome have been reported. Two cases resembling the phenotype but with no causative variants in SCARF2 have been reported, supporting the possibility of another causative gene with overlapping phenotype. Though prognosis can often be positive, there is a need for better long-term outcome data.\u0000 </div>","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":"200 11","pages":"2472-2479"},"PeriodicalIF":1.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148029","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

Refining Domain-Based Prognostication in DNM1 Encephalopathy: A Mild Phenotype Associated With a GTPase Domain Variant 改进DNM1脑病基于结构域的预后：与GTPase结构域变异相关的轻度表型。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2026-10-09 Epub Date: 2026-06-12 DOI: 10.1002/ajmg.a.70226

Caroline Crain, Hope Northrup, Laura S. Farach, Sureni V. Mullegama, Kathleen Shields, Gretchen Von Allmen, Kate Richardson

{"title":"Refining Domain-Based Prognostication in DNM1 Encephalopathy: A Mild Phenotype Associated With a GTPase Domain Variant","authors":"Caroline Crain, Hope Northrup, Laura S. Farach, Sureni V. Mullegama, Kathleen Shields, Gretchen Von Allmen, Kate Richardson","doi":"10.1002/ajmg.a.70226","DOIUrl":"10.1002/ajmg.a.70226","url":null,"abstract":"DNM1 encephalopathy is a rare autosomal dominant genetic condition characterized by a range of neurological and developmental manifestations. The typical phenotype is severe, including profound intellectual disability, treatment-resistant epilepsy, ataxia, and structural brain abnormalities. However, milder presentations have increasingly been reported, suggesting that the full phenotypic spectrum remains incompletely defined. We describe the case of a female patient who presents only with well-controlled epilepsy and mild dysmorphic features. Trio exome sequencing identified a de novo likely pathogenic variant in the GTPase domain of DNM1, supporting the diagnosis of DNM1 encephalopathy. Historically, disease-causing variants in the GTPase domain were thought to confer a more severe presentation. However, our patient demonstrates a more attenuated phenotype than previously reported cases, including those viewed as mild, which have consistently included some degree of developmental impairment. This supports an expanded and more variable phenotypic spectrum of DNM1 encephalopathy than previously recognized. This additionally complicates domain-based prognostication; though further cases will aid in elucidating genotype–phenotype correlation.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":"200 11","pages":"2558-2561"},"PeriodicalIF":1.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.a.70226","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148238414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assessment of Growth in Cardio-Facio-Cutaneous Syndrome 心-面-皮综合征的生长评估。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2026-10-09 Epub Date: 2026-05-28 DOI: 10.1002/ajmg.a.70218

Kari Johnston, Sandesh C. S. Nagamani, Bradley S. Miller, Katherine A. Rauen, Richard D. Boyce, Salma Musaad, Pilar L. Magoulas

{"title":"Assessment of Growth in Cardio-Facio-Cutaneous Syndrome","authors":"Kari Johnston, Sandesh C. S. Nagamani, Bradley S. Miller, Katherine A. Rauen, Richard D. Boyce, Salma Musaad, Pilar L. Magoulas","doi":"10.1002/ajmg.a.70218","DOIUrl":"10.1002/ajmg.a.70218","url":null,"abstract":"Cardio-facio-cutaneous (CFC) syndrome is a rare, multiple congenital anomaly disorder in which individuals commonly experience faltering growth; however, systematic analysis of growth parameters in this disorder has not been performed. We recruited 69 participants with CFC through CFC International and collected data on assessing height, weight, and body mass index (BMI). We found that the height-for-age and weight-for-age Z-scores were consistently lower in individuals with CFC than in the reference population and that children with CFC experience growth restriction from infancy to adulthood. Our findings show that as individuals age, their height Z-scores remain constant (−2 to −3 SD). However, over time, their weight shows a progressive decrease from average. There were no significant differences between the mean Z-scores of the growth parameters based on an individual's history of enteral feeding, gene associated with diagnosis, nor growth hormone deficiency status. This implies that feeding modality and severity of feeding difficulties may not be directly related to growth. Other factors could be responsible, such as malabsorption of nutrients, constitutional growth delay, hormonal deficiencies or resistance, or cardiac abnormalities. Our study is one of the first to systematically characterize growth parameters and analyze the association of clinical covariates with these parameters in individuals with CFC syndrome. Accurate assessment of growth in this rare condition will allow providers to recognize outliers of growth in their patients with CFC when compared to other individuals with CFC and make necessary referrals and recommendations, which may ultimately improve outcomes.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":"200 11","pages":"2443-2453"},"PeriodicalIF":1.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.a.70218","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expanded Phenotype Associated With an Intronic PPP1R12A Variant: A Case Report and Literature Review 扩展表型与内含子PPP1R12A变异相关：一个病例报告和文献综述。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2026-10-09 Epub Date: 2026-05-24 DOI: 10.1002/ajmg.a.70212

Emily M. Bland, Amber Nakar Weinstein, Eric C. Kao, Xiaonan Zhao, Monika Weisz-Hubshman

{"title":"Expanded Phenotype Associated With an Intronic PPP1R12A Variant: A Case Report and Literature Review","authors":"Emily M. Bland, Amber Nakar Weinstein, Eric C. Kao, Xiaonan Zhao, Monika Weisz-Hubshman","doi":"10.1002/ajmg.a.70212","DOIUrl":"10.1002/ajmg.a.70212","url":null,"abstract":"Autosomal dominant PPP1R12A-related genitourinary and/or brain malformation syndrome is a recently described multisystem disorder caused by loss-of-function variants in the protein phosphatase 1 regulatory subunit 12a (PPP1R12A) gene. To date, 22 affected individuals have been reported with variable brain malformations and genitourinary anomalies, including differences of sexual development. Of these cases, four probands had anomalies involving both organ systems. Here, we report a 12-year-old individual with global developmental delay, semi-lobar holoprosencephaly, microcephaly, spastic quadriplegia, bilateral polydactyly, and ambiguous genitalia. The proband was found to have a 46,XY chromosome complement. Trio genome sequencing with sequential RNA sequencing revealed a novel intronic variant that generates an out-of-frame transcript with a premature stop codon, supporting a loss-of-function mechanism. We review previously reported cases of PPP1R12A-related disease and summarize genotypes and frequency of reported clinical features, further illustrating the variable expressivity associated with this condition. Our findings broaden the phenotypic and genotypic spectrum of PPP1R12A and reinforce the role of transcript-level analysis in the evaluation of suspected splicing variants.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":"200 11","pages":"2519-2524"},"PeriodicalIF":1.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.a.70212","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2026-10-09 Epub Date: 2026-05-31 DOI: 10.1002/ajmg.a.70222

Ayako Konishi, Makiko Tachibana, Yuji Oto, Kenichi Kashimada, Tomohiro Ishii, Yoko Aoki, Koji Muroya, Yutaka Takahashi, Kenji Kurosawa, Tsutomu Ogata, Masanobu Kawai

{"title":"Health-Related Quality of Life and Its Related Factors in Adolescents and Adults With Prader–Willi Syndrome in Japan","authors":"Ayako Konishi, Makiko Tachibana, Yuji Oto, Kenichi Kashimada, Tomohiro Ishii, Yoko Aoki, Koji Muroya, Yutaka Takahashi, Kenji Kurosawa, Tsutomu Ogata, Masanobu Kawai","doi":"10.1002/ajmg.a.70222","DOIUrl":"10.1002/ajmg.a.70222","url":null,"abstract":"<div>\u0000 \u0000 Prader–Willi syndrome (PWS) is a rare neurogenetic disorder characterized by endocrine, metabolic, behavioral, and psychiatric features. These manifestations may affect health-related quality of life (HRQOL). Evidence on HRQOL in adolescents and adults with PWS remains limited. This study evaluated HRQOL and examined sex, age, genetic, and behavioral factors associated with HRQOL in individuals with genetically confirmed PWS aged 16 years and over. A proxy-reported questionnaire survey was conducted through a Japanese national PWS support group, and responses from 119 participants (median age, 25 years) were analyzed. The primary outcome was a EuroQol five-dimension five-level (EQ-5D-5L) index value in the upper tertile of the study distribution (≥ 0.744). The median EQ-5D-5L index value was 0.665 (IQR, 0.549–0.775), and the mean was 0.652 (SD, 0.180). Only 4.3% of participants reported no problems in any dimension. Younger age (16–19 years) (OR, 4.62; 95% CI, 1.42–15.1), the deletion genetic subtype (4.79; 1.15–20.0), and lower problematic food-related behaviors (0.90; 0.83–0.97) were independently associated with an EQ-5D-5L index value in the upper tertile. Support during the transition from late adolescence to early adulthood and attention to problematic food-related behaviors may be important for improving the HRQOL of individuals with PWS.\u0000 </div>","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":"200 11","pages":"2464-2471"},"PeriodicalIF":1.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136496","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

Adult Case of Stüve–Wiedemann Syndrome 成人<s:1> ve- wiedemann综合征1例。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2026-10-09 Epub Date: 2026-05-24 DOI: 10.1002/ajmg.a.70214

Christina Kelly, Megan Morand, Joseph W. Ray

{"title":"Adult Case of Stüve–Wiedemann Syndrome","authors":"Christina Kelly, Megan Morand, Joseph W. Ray","doi":"10.1002/ajmg.a.70214","DOIUrl":"10.1002/ajmg.a.70214","url":null,"abstract":"<div>\u0000 \u0000 Stüve–Wiedemann Syndrome (SWS) is a rare autosomal recessive skeletal dysplasia caused by variations in the leukemia inhibitory factor receptor (LIFR) gene. Due to its high rate of mortality in early life, current literature is largely limited to children with SWS. We present a case report of a 35-year-old female with SWS, one of the few documented adults with SWS. She was diagnosed at age 34 after clinical exome sequencing identified homozygous pathogenic variants in LIFR at c.756dup (p.Lys253*), a known pathogenic variant associated with SWS. Her past medical history consists of feeding and respiratory difficulties in infancy, recurrent fractures, a deep vein thrombosis of the upper extremity, osteoporosis, and an incidental finding of a brain aneurysm. Of note, she has undergone over 25 surgeries without complications from anesthesia. As an adult, her symptoms include heart palpitations, fatigue, restless leg syndrome, temperature dysregulation, poor dentition, and bone fragility. On physical exam, she displays short stature, blue sclera, kyphoscoliosis, significant loss of range of motion in multiple joints, and fusions in the fingers and toes. To our knowledge, she is the oldest reported individual in the literature with SWS, and her case provides insight into how symptoms evolve over time.\u0000 </div>","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":"200 11","pages":"2525-2528"},"PeriodicalIF":1.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013121","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