American Journal of Medical Genetics Part A最新文献_第5页

Systematic Review of Females With Intellectual Disability and MECP2 Duplication. 智力残疾女性与MECP2重复的系统综述。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2026-10-08 DOI: 10.1002/ajmg.a.70318

Paul Malik, Davut Pehlivan, Cary Fu, Antonio F Martinez-Monseny, Mar O'Callaghan, Judith Armstrong, Sarika U Peters, Steven T Lee, Timothy J Feyma, Paola Mian, Christine Coquery

{"title":"Systematic Review of Females With Intellectual Disability and MECP2 Duplication.","authors":"Paul Malik, Davut Pehlivan, Cary Fu, Antonio F Martinez-Monseny, Mar O'Callaghan, Judith Armstrong, Sarika U Peters, Steven T Lee, Timothy J Feyma, Paola Mian, Christine Coquery","doi":"10.1002/ajmg.a.70318","DOIUrl":"https://doi.org/10.1002/ajmg.a.70318","url":null,"abstract":"MECP2 Duplication Syndrome (MDS) is a rare, X-linked neurodevelopmental disorder typically affecting males. Females with MDS have been reported and are compiled here. We conducted a systematic review (PROSPERO CRD420250652426) of PubMed, EMBASE, and Google Scholar extracting individual participant data. Inclusion required confirmed full MECP2 gene duplication and evidence of ID (IQ < 75 or significant deficits in adaptive functioning). Affected females were compared with a published male MDS dataset, stratified by genetic variant. From 590 full-texts, 41 unique female records were included. Tandem duplications were most frequent (59%), followed by unbalanced autosomal translocations (32%), other terminal duplications (7.3%), and one triplication. Most tandem duplication females exhibited skewed X-inactivation (14/18 reports) and presented with mild-to-moderate developmental delay, partially retained speech and ambulation (all but one report), and fewer neurological/systemic manifestations relative to male counterparts. Females with unbalanced translocations or other terminal duplications had severe ID, absent speech (5/9 reports), and severe epilepsy (8/16 reports included drug-resistant epilepsy). Features included respiratory infections (12/14), feeding problems (8/11), microcephaly (10/14), and shortened survival. Affected females show genotype-dependent severity: tandem duplications were associated with broader, generally less severe phenotypes and variable epilepsy expression, whereas severe translocation/terminal duplication females may resemble male MDS.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134802","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

TTC21B: From Modifier to Causative Gene in Joubert Syndrome. TTC21B：从Joubert综合征的修饰基因到致病基因。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2026-10-08 DOI: 10.1002/ajmg.a.70319

Valentina Serpieri, Fulvio D'Abrusco, Anna Pichiecchio, Thouraya Ben Younes, Ichraf Kraoua, Enza Maria Valente

引用次数: 0

The Value of Integrating Adult Genetic Services Into Pregnancy Care: Changing Fetal, Neonatal, and Maternal Management. 将成人遗传服务纳入妊娠护理的价值：改变胎儿、新生儿和产妇管理。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2026-10-08 DOI: 10.1002/ajmg.a.70329

Madeline J Dyke, Emily E Hardisty, Neeta L Vora, Asha N Talati

{"title":"The Value of Integrating Adult Genetic Services Into Pregnancy Care: Changing Fetal, Neonatal, and Maternal Management.","authors":"Madeline J Dyke, Emily E Hardisty, Neeta L Vora, Asha N Talati","doi":"10.1002/ajmg.a.70329","DOIUrl":"https://doi.org/10.1002/ajmg.a.70329","url":null,"abstract":"Adult patients with known or suspected genetic diagnoses face unique challenges in accessing care that informs pregnancy management and reproductive decision-making. To address this gap, we established an Adult Genetics & Reproductive Health Clinic (AGRH). We conducted a retrospective study of 112 patients evaluated between July 2022 and September 2025. Demographics, referral characteristics, genetic testing, and effects of testing on maternal, fetal, pregnancy care, and familial care were reviewed. Fifty-nine patients (53%) were seen preconception and 53 (47%) during pregnancy. Seventy-five patients (67%) were offered diagnostic genetic testing; 58 (77%) completed testing and 17 (23%) declined. Among the 58 patients completing testing, 20 (35%) received a diagnostic result, including 10 new molecular diagnoses and 10 results confirming a suspected or established clinical diagnosis; two additional patients had incidental findings. Thirty-six patients (62%) had negative results, including 11 informative negative results that excluded the suspected condition and informed care. Overall, 33 of 58 patients (56.9%) had results that informed clinical care through a new or confirmed diagnosis, incidental finding, or informative negative result. Integration of adult genetic evaluation into reproductive healthcare frequently informs pregnancy management, reproductive planning, and familial care.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134797","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

Height, Head Circumference, Sitting Height, Leg Length, and Body Proportions Growth References to the Argentinian and Spanish Population for Hypochondroplasia. 身高、头围、坐高、腿长和身体比例：阿根廷和西班牙人群软骨发育不全的参考资料。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2026-10-07 DOI: 10.1002/ajmg.a.70325

Mariana Del Pino, Mercedes León-López, Sofía Chiaramonte, Silvia Modamio-Hoybjor, Ana C Barreda-Bonis, Verónica Araoz, Silvia Caino, Rosario Ramos-Mejía, Karen E Heath

{"title":"Height, Head Circumference, Sitting Height, Leg Length, and Body Proportions Growth References to the Argentinian and Spanish Population for Hypochondroplasia.","authors":"Mariana Del Pino, Mercedes León-López, Sofía Chiaramonte, Silvia Modamio-Hoybjor, Ana C Barreda-Bonis, Verónica Araoz, Silvia Caino, Rosario Ramos-Mejía, Karen E Heath","doi":"10.1002/ajmg.a.70325","DOIUrl":"https://doi.org/10.1002/ajmg.a.70325","url":null,"abstract":"Hypochondroplasia (HCH) is a rare autosomal dominant skeletal dysplasia caused by gain-of-function variants in FGFR3, leading to disproportionate short stature. Available growth references are limited, and body proportion data is lacking. We conducted a retrospective cohort study of 131 children with molecularly confirmed HCH (72 males, 59 females) from Argentina and Spain. Longitudinal anthropometric data (height, sitting height, head circumference) from birth to 18 years were analyzed. Leg length and body proportion indices were derived. Age- and sex-specific centiles were constructed using the LMS method. A total of 864 height, 660 sitting height, and 777 head circumference measurements were included. The majority of the individuals had the recurrent p.Asn540Lys FGFR3 variant (116/131). Birth size was significantly lower than reference standards. Height remained below the general population, with an overlap between the third centile of reference charts and the 90th-97th centiles of HCH. Sitting height showed a mild pubertal spurt, while leg length was markedly reduced without pubertal acceleration. Head circumference was normal but relatively increased for height. Body proportion indices confirmed disproportion from early life. These new growth references, including segmental and proportional indices, provide clinically relevant tools for monitoring growth and evaluating emerging therapies in HCH.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126162","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

Fracture Prevalence Among Those With Hypermobility Spectrum Disorder/Hypermobile Ehlers-Danlos Syndrome. 多活动谱系障碍/多活动埃勒-丹洛斯综合征患者骨折患病率

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2026-10-07 DOI: 10.1002/ajmg.a.70324

Brad T Tinkle

{"title":"Fracture Prevalence Among Those With Hypermobility Spectrum Disorder/Hypermobile Ehlers-Danlos Syndrome.","authors":"Brad T Tinkle","doi":"10.1002/ajmg.a.70324","DOIUrl":"https://doi.org/10.1002/ajmg.a.70324","url":null,"abstract":"Previous series have questioned bone fragility in those with hypermobility spectrum disorders (HSD) or hypermobile Ehlers-Danlos syndrome (hEDS). These conclusions have been extrapolated to infants and children often in the setting of suspected child abuse. Few studies address this in non-ambulatory children, leaving medical professionals and the courts alike to debate the reported observations. One hundred patients with HSD/hEDS were recruited from a large hypermobility clinic. Each was required to have a guardian/parent present to attest to the fracture history for the entire age of the individual. Each was asked for the number of fractures, age at incident for each, and qualitative data regarding the mechanism of injury. Those experiencing a fracture in their lifetime were 55.6% (55/99). Only two fractures were recorded in the infantile period. There was only one rib fracture from trauma and no skull fractures. While fracture prevalence was higher than expected in ambulatory individuals with HSD/hEDS, no fractures occurred within the first year of life not known from the birthing process. The pattern of fractures was consistent with that normally seen in childhood. Qualitative data suggest no significant evidence of fragility fractures, especially in non-ambulatory children.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126206","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

Correction to "Unraveling a Diagnostic Enigma: A TECPR2 Case Solved Through Multi-Omic Genomics". 更正“解开诊断之谜：通过多组基因组学解决TECPR2病例”。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2026-10-06 DOI: 10.1002/ajmg.a.70312

引用次数: 0

Clinical Spectrum, Genetic Profile, and Genotype-Phenotype Correlations in Microvillus Inclusion Disease: A Systematic Review. 微绒毛包涵性疾病的临床谱、遗传谱和基因型-表型相关性：系统综述。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2026-10-05 DOI: 10.1002/ajmg.a.70314

Xiang Pan, Zhi-Jun Mo, Hui Lin, Jing-Jing Ma, Yuan-Zong Song

{"title":"Clinical Spectrum, Genetic Profile, and Genotype-Phenotype Correlations in Microvillus Inclusion Disease: A Systematic Review.","authors":"Xiang Pan, Zhi-Jun Mo, Hui Lin, Jing-Jing Ma, Yuan-Zong Song","doi":"10.1002/ajmg.a.70314","DOIUrl":"https://doi.org/10.1002/ajmg.a.70314","url":null,"abstract":"Microvillus inclusion disease (MVID) is a rare congenital enteropathy caused by defects in intestinal epithelial apical trafficking and polarity. Although its genetic basis is well established, the clinical spectrum and genotype-phenotype correlations remain incompletely defined. We aimed to systematically characterize the clinical and genetic features of MVID and investigate genotype-phenotype correlations. A systematic review of MVID literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, with database searches performed from inception to August 5, 2026. A total of 118 studies comprising 336 patients were included. Intractable diarrhea was reported in 98.8% (332/336). Extraintestinal involvement was documented in 243 patients and was most often hepatic (127/243, 52.3%), with cholestasis in 80/127 (63.0%), cirrhosis in 16/127 (12.6%), and hepatic failure in 8/127 (6.3%). Among 287 patients with treatment data, 280 (97.6%) received total parenteral nutrition (TPN). Management patterns changed across reporting eras, with intestinal transplantation reported in 33.3% (23/69) of patients in 1996-2010 and 12.9% (16/124) in 2011-2026. Pathogenic variants were identified most commonly in MYO5B, followed by STXBP2, STX3, and UNC45A. Bi-allelic null MYO5B variants were associated with earlier onset than bi-allelic non-null variants (p < 0.001); in severe hepatic involvement, the presence of at least one null MYO5B variant was associated with reduced liver-intestine transplant-free survival (log-rank p = 0.040). MVID is characterized by intractable diarrhea and substantial hepatic involvement. Molecular diagnosis clarifies the genetic etiology and provides a basis for genotype-informed clinical stratification. Treatment strategies should be interpreted in an era-specific context. Systematic Review Registration: PROSPERO (CRD42024503464).","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102624","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

Expanding the Phenotypic Spectrum of TXNDC15-Related Ciliopathies to Include Joubert Syndrome. 扩大txndc15相关纤毛病的表型谱，包括Joubert综合征。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2026-10-05 DOI: 10.1002/ajmg.a.70317

Zachary T Sentell, Robert Geraghty, Juliana E Arcila-Galvis, Praveen Dhondurao-Sudhindar, Sergio Foullerat Cañada, Fulvio D'Abrusco, Bosanka Jocic-Jakubi, Miguel Barroso-Gil, Valentina Serpieri, Thomas M Kitzler, Kate E Chandler, Eleanor G Seaby, Gabrielle Wheway, Jennifer C Dempsey, Dan Doherty, Enza M Valente, John A Sayer

{"title":"Expanding the Phenotypic Spectrum of TXNDC15-Related Ciliopathies to Include Joubert Syndrome.","authors":"Zachary T Sentell, Robert Geraghty, Juliana E Arcila-Galvis, Praveen Dhondurao-Sudhindar, Sergio Foullerat Cañada, Fulvio D'Abrusco, Bosanka Jocic-Jakubi, Miguel Barroso-Gil, Valentina Serpieri, Thomas M Kitzler, Kate E Chandler, Eleanor G Seaby, Gabrielle Wheway, Jennifer C Dempsey, Dan Doherty, Enza M Valente, John A Sayer","doi":"10.1002/ajmg.a.70317","DOIUrl":"https://doi.org/10.1002/ajmg.a.70317","url":null,"abstract":"Biallelic loss-of-function variants in TXNDC15 are a known cause of the perinatally lethal ciliopathy Meckel syndrome (MKS). TXNDC15 encodes an endoplasmic reticulum (ER)-resident thioredoxin-domain protein required for ciliary transition zone integrity. Many ciliopathy genes show a spectrum of severity, producing a clinical continuum from lethal MKS to the less severe Joubert syndrome (JS). Using genome and exome sequencing analysis, we identified four unrelated children with JS who harbor rare biallelic variants in TXNDC15. In contrast to the biallelic truncating variants typical of MKS, all individuals with JS carried a missense variant in trans with a truncating variant. Three of four missense variants cluster within the functionally critical thioredoxin domain. In silico structural modeling using AlphaFold and variant effect prediction (AlphaMissense, DynaMut2) support a deleterious effect on protein stability and function for the majority of these missense variants. This work expands the phenotypic spectrum of TXNDC15-related ciliopathies to include JS. All four individuals carried a missense allele in trans with a truncating allele. Our findings underscore the importance of including TXNDC15 in the genetic diagnosis of JS.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102758","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

Fatal Dilated Cardiomyopathy and Monogenic Diabetes Mellitus as SMPD4-Related Disorder. 致死性扩张型心肌病和单基因糖尿病作为smpd4相关疾病。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2026-10-04 DOI: 10.1002/ajmg.a.70323

Takato Akiba, Shino Shimada, Ken Takahashi, Akimi Ishikawa, Naoko Hiramatsu, Kanato Iwahara, Mizuki Inage, Mamiko Yamada, Kenjiro Kosaki, Hiromichi Shoji

{"title":"Fatal Dilated Cardiomyopathy and Monogenic Diabetes Mellitus as SMPD4-Related Disorder.","authors":"Takato Akiba, Shino Shimada, Ken Takahashi, Akimi Ishikawa, Naoko Hiramatsu, Kanato Iwahara, Mizuki Inage, Mamiko Yamada, Kenjiro Kosaki, Hiromichi Shoji","doi":"10.1002/ajmg.a.70323","DOIUrl":"https://doi.org/10.1002/ajmg.a.70323","url":null,"abstract":"Sphingomyelin phosphodiesterase 4 (SMPD4)-related disorder is a rare neurodevelopmental disorder caused by biallelic loss-of-function variants in SMPD4, characterized primarily by severe neurological manifestations. A subset of long-term survivors develops diabetes mellitus (DM); however, the progression of systemic complications, including cardiomyopathy, remains poorly understood. In this report, we describe serial clinical observations over 5 years in a previously described child with SMPD4-related disorder. At 6 years of age, following an infectious episode, the boy was diagnosed with autoantibody-negative DM and dilated cardiomyopathy (DCM). DM was characterized by progressively increasing insulin requirements due to impaired insulin secretion, leading to the diagnosis of monogenic diabetes associated with SMPD4 deficiency. Serial echocardiographic findings revealed consistent DCM progression, characterized by left ventricular dilatation, myocardial wall thinning, and reduced fractional shortening, accompanied by recurrent infection-triggered exacerbations that ultimately resulted in advanced DCM. This case suggests that SMPD4-related disorder can manifest as progressive DM/DCM post-infancy. This report is the first longitudinal DCM description, underscoring multisystem involvement and the need for lifelong metabolic and cardiac monitoring, particularly during periods of infection-triggered exacerbations.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102761","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

Temple Syndrome Is a Frequent Differential Diagnosis of Silver-Russell Syndrome, but Infrequently Suspected in Chile. 太阳穴综合征是银罗素综合征的常见鉴别诊断，但在智利很少被怀疑。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2026-10-01 Epub Date: 2026-05-07 DOI: 10.1002/ajmg.a.70193

Macarena Tobar, Fernanda Martín, Paulina Morales, Ángela Peña, Paola Acevedo, Carola Goecke-Hochberger, Sebastián Silva-Soto, Víctor Faundes, Lorena Santa María

引用次数: 0