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

Second Report of the p.Leu874Pro Missense Variant in EPHB4 in a Family With Capillary Malformation-Arteriovenous Malformation Syndrome (CM-AVM) Syndrome. 毛细血管畸形-动静脉畸形综合征（CM-AVM）家族中 EPHB4 p.Leu874Pro 缺义变异的第二次报告

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-21 DOI: 10.1002/ajmg.a.63898

Laura E Goeser, Leah Lalor, Yvonne E Chiu, Michael Muriello

引用次数: 0

Clinical Features of a Japanese Girl With Radio-Tartaglia Syndrome due to a SPEN Truncating Variant. 一名因 SPEN 截短变异体而患有无线电-塔塔利亚综合征的日本女孩的临床特征。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-21 DOI: 10.1002/ajmg.a.63910

Eriko Nishi, Kumiko Yanagi, Nobuhiko Okamoto, Tadashi Kaname

{"title":"Clinical Features of a Japanese Girl With Radio-Tartaglia Syndrome due to a SPEN Truncating Variant.","authors":"Eriko Nishi, Kumiko Yanagi, Nobuhiko Okamoto, Tadashi Kaname","doi":"10.1002/ajmg.a.63910","DOIUrl":"https://doi.org/10.1002/ajmg.a.63910","url":null,"abstract":"Radio-Tartaglia syndrome (RATARS) (MIM#619312) is a genetic disorder caused by heterozygous truncating variants of SPEN on chromosome 1p36. This syndrome is extremely rare, with only 34 cases reported to date. RATARS is characterized by developmental delay, hypotonia, and intellectual disability. In this study, we report a Japanese girl with psychomotor delay, hypotonia, and facial features resembling Down syndrome (DS). We identified a de novo heterozygous pathogenic variant of SPEN and diagnosed her with RATARS. The patient was born at 38 weeks and 1 day of gestational age, weighing 2598 g, without respiratory or feeding difficulties. We first considered DS as a differential diagnosis based on the developmental delay with hypotonia and facial features, including an upslanted palpebral fissure, hypertelorism, epicanthus folds, and a low nose; however, it was ruled out after cytogenetic testing. Microarray analysis revealed no pathogenic aberrations. We performed trio-based whole exome sequencing and identified a recurrent pathogenic variant of SPEN:NM_015001.3:c.6223_6227del, p.(Ser2075GlufsTer46). Although some features of RATARS have been reported to be similar to those of 1p36 deletion syndrome, facial similarity to DS was a characteristic of our case. Whether this feature is unique to the patient or relatively common in individuals with RATARS should be discussed further as more cases of individuals with RATARS are reported.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455913","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

A Prevalent TMEM260 Deletion Causes Conotruncal Heart Defects, Including Truncus Arteriosus. 普遍的 TMEM260 基因缺失会导致脐带绕心缺陷，包括动脉导管未闭。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-19 DOI: 10.1002/ajmg.a.63906

Naoya Saijo, Hisao Yaoita, Jun Takayama, Chiharu Ota, Eiichiro Kawai, Masato Kimura, Akira Ozawa, Gen Tamiya, Shigeo Kure, Atsuo Kikuchi

{"title":"A Prevalent TMEM260 Deletion Causes Conotruncal Heart Defects, Including Truncus Arteriosus.","authors":"Naoya Saijo, Hisao Yaoita, Jun Takayama, Chiharu Ota, Eiichiro Kawai, Masato Kimura, Akira Ozawa, Gen Tamiya, Shigeo Kure, Atsuo Kikuchi","doi":"10.1002/ajmg.a.63906","DOIUrl":"https://doi.org/10.1002/ajmg.a.63906","url":null,"abstract":"Conotruncal heart defects are severe congenital malformations of the outflow tract, including truncus arteriosus (TA) and double-outlet right ventricle (DORV). TA is a severe congenital heart disease (CHD) in which the main arterial outflow tract of the heart fails to separate. We recently reported TMEM260 (NM_017799.4), c.1617del (p.Trp539Cysfs*9), as a major cause of TA in the Japanese population (TMEM260 Keio-Tohoku variant) comparable to the prevalence of the 22q11.2 deletion syndrome, which accounts for 12%-35% of TA. However, no other major causes of TA have not been identified. Here, we report a family that included a TA patient and a DORV patient, harboring the compound heterozygous variants of TMEM260, a 7066-bp deletion encompassing exons 6-7 and c.1393C > T, p.(Gln465*). The allele frequency of the 7066-bp deletion was particularly high in the Japanese population (0.17%). Based on the allele frequency of this deletion and c.1617del (0.36%) in the Japanese population, TMEM260 variants might be associated with more than half of the Japanese patients with TA. This study showed that TMEM260 pathogenic variants might be the most common cause of TA in the Japanese population and could explain the wide spectrum of phenotypes associated with TMEM260-related CHD, including DORV, demonstrating the usefulness of genetic testing in Japanese patients with TA.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455908","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 Phenotype of NRROS-Related SENEBAC Syndrome. 扩展与 NRROS 相关的 SENEBAC 综合征的表型。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-18 DOI: 10.1002/ajmg.a.63899

Varunvenkat M Srinivasan, Vykuntaraju K Gowda, Annsmol P Markose, Uddhava V Kinhal, Himani Pandey

引用次数: 0

Exome Sequencing Detects Uniparental Disomy of Chromosome 4 Revealing a LARP7 Pathogenic Variant Responsible for Alazami Syndrome: A Case Report. 外显子组测序发现 4 号染色体单亲缺失，揭示了导致阿拉扎米综合征的 LARP7 致病变体：病例报告。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-17 DOI: 10.1002/ajmg.a.63891

Buisine-Sbraggia Amélie, Thevenon Julien, Yauy Kevin, Naud Marie-Emmanuelle, Costa Jean-Marc, Dubois-Teklali Fanny, Willems Marjolaine, Dieterich Klaus, Satre Véronique, Coutton Charles, Le Tanno Pauline

{"title":"Exome Sequencing Detects Uniparental Disomy of Chromosome 4 Revealing a LARP7 Pathogenic Variant Responsible for Alazami Syndrome: A Case Report.","authors":"Buisine-Sbraggia Amélie, Thevenon Julien, Yauy Kevin, Naud Marie-Emmanuelle, Costa Jean-Marc, Dubois-Teklali Fanny, Willems Marjolaine, Dieterich Klaus, Satre Véronique, Coutton Charles, Le Tanno Pauline","doi":"10.1002/ajmg.a.63891","DOIUrl":"https://doi.org/10.1002/ajmg.a.63891","url":null,"abstract":"Alazami syndrome is an autosomal recessive disease characterized by global developmental delay, growth restriction, and distinctive facial features. Fewer than 50 individuals are currently reported with biallelic loss of function variants in LARP7. We report the case of a 3.5-year-old boy born from nonconsanguineous parents, presenting with syndromic global developmental delay. Exome sequencing identified a homozygous frameshift pathogenic variant in LARP7. Parental analysis failed to detect the variant in the paternal sample, although the father's biological paternity was confirmed. Targeted secondary bioinformatic analyses at the LARP7 locus suggested a 45 Mb loss of heterozygosity (LOH), further confirmed by a single nucleotide polymorphism array that identified four LOH regions on chromosome 4, including one encompassing LARP7. This LOH exposes the recessive LARP7 pathogenic variant, resulting in the manifestation of Alazami syndrome. To our knowledge, this is the first reported case of Alazami syndrome due to uniparental disomy (UPD). UPD is a rare cause of autosomal recessive disorders. Its identification is crucial for genetic counseling to adjust recurrence risk for siblings. This case highlights the effectiveness and usefulness of bioinformatics algorithms applied to next generation sequencing in detecting such events.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455914","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

KIF11 Variants Associated With Novel Renal System Involvement-Two Cases That Expand the Phenotypic Spectrum of Microcephaly With or Without Chorioretinopathy, Lymphedema, or Impaired Intellectual Development. 与新型肾脏系统受累有关的 KIF11 变异--两例扩大了伴有或不伴有脉络膜视网膜病变、淋巴水肿或智力发育受损的小头畸形的表型范围。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-15 DOI: 10.1002/ajmg.a.63903

Tessa Gonzalez, Rebecca C Tyler, Kala F Schilter, Julie McCarrier, Michael Muriello, Donald Basel, Honey V Reddi

引用次数: 0

An Unusual Presentation of Leber Hereditary Optic Neuropathy-Plus Case Caused by a Novel DNAJC30 Variant. 由新型 DNAJC30 变体引起的勒伯遗传性视神经病变（Leber Hereditary Optic Neuropathy-Plus）病例的不寻常表现。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-15 DOI: 10.1002/ajmg.a.63902

Hüseyin Bahadır Şenol, Didem Soydemir, Ayşe İpek Polat, Adem Aydın, Ayşe Semra Hız, Uluç Yiş

{"title":"An Unusual Presentation of Leber Hereditary Optic Neuropathy-Plus Case Caused by a Novel DNAJC30 Variant.","authors":"Hüseyin Bahadır Şenol, Didem Soydemir, Ayşe İpek Polat, Adem Aydın, Ayşe Semra Hız, Uluç Yiş","doi":"10.1002/ajmg.a.63902","DOIUrl":"https://doi.org/10.1002/ajmg.a.63902","url":null,"abstract":"Leber hereditary optic neuropathy (LHON) is characterized by vision loss due to the degeneration of retinal ganglion cells. LHON-Plus refers to LHON with additional extraocular findings. Neurological conditions observed in LHON-Plus include seizures, encephalopathy, movement disorders, neuropathy, and myopathy. Herein, we present a case with atypical LHON-Plus caused by a novel DNAJC30 disease-causing gene variant. A 15-year-old boy presented with acute headache, and blurred and decreased vision in both eyes. Although initial evaluation pointed toward idiopathic intracranial hypertension, the subsequent diagnostic process revealed unusual features like area postrema syndrome and T2 hyperintensity in brain magnetic resonance imaging. Consequently, antibody-negative neuromyelitis optica spectrum disorder (NMOSD) was diagnosed and treatment was commenced. Recurrent episodes of elevated intracranial pressure necessitated the insertion of a ventriculoperitoneal shunt. Exome sequencing (ES) revealed a novel homozygous variant in the DNAJC30 gene 2 years after symptom onset. Atypical LHON presentations due to nuclear gene mutations may mimic other neuroinflammatory conditions like NMOSD, necessitating thorough clinical evaluation and genetic testing. ES plays a crucial role in diagnosing complex neurological cases, enabling the identification of novel genetic variants associated with LHON and related disorders.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455910","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

KBG Syndrome in 16 Indian Individuals. 16 名印度人的 KBG 综合征

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-15 DOI: 10.1002/ajmg.a.63907

Shruti Bajaj, Sheela Nampoothiri, Roshni Chugh, Jayesh Sheth, Frenny Sheth, Harsh Sheth, Vinu Narayan, Ameya Deshpande, Anaita Hegde, Aradhana Dwivedi, Dhanya Yeshodharan, Indu Khosla, Madhukar Mittal, Mahesh Kore, Vedam Ramprasad, Anbu Kayalvizhi C, Katta M Girisha

{"title":"KBG Syndrome in 16 Indian Individuals.","authors":"Shruti Bajaj, Sheela Nampoothiri, Roshni Chugh, Jayesh Sheth, Frenny Sheth, Harsh Sheth, Vinu Narayan, Ameya Deshpande, Anaita Hegde, Aradhana Dwivedi, Dhanya Yeshodharan, Indu Khosla, Madhukar Mittal, Mahesh Kore, Vedam Ramprasad, Anbu Kayalvizhi C, Katta M Girisha","doi":"10.1002/ajmg.a.63907","DOIUrl":"https://doi.org/10.1002/ajmg.a.63907","url":null,"abstract":"We aimed to describe the clinical and genetic characteristics of 16 individuals with KBG syndrome (KBGS) from 13 Indian families. We retrospectively analyzed the clinical details of individuals with KBGS harboring a likely pathogenic/pathogenic variant in ANKRD11. We also analyzed their facial gestalt using Face2Gene and recorded the top three differential disorders suggested by the application. The most frequent clinical features observed in our cohort were as follows: learning and intellectual disability-14/15 (93%), skeletal abnormalities-14/15 (93%), postnatal short stature-13/15 (87%), brachydactyly-11/15 (73%), and characteristic facial appearance-13/15 (87%). We identified 12 single nucleotide variants (SNVs), including six recurrent and six novel variants, and a copy number variant in the 16q24.3 region encompassing ANKRD11 gene. The novel variants were as follows: p.(Gln1236Ter), p.(Asp884ThrfsTer93), p.(Arg1466GlyfsTer87), p.(Tyr2056Ter), p.(Leu955TrpfsTer22), and p.(Lys766ArgfsTer10). The identified SNVs in ANKRD11 clustered around exon 9. We observed a high concordance of Face2Gene in predicting KBGS.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455916","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

Cerebellar Hypoplasia and Treatment Course of a Two-Month-Old Infant With KCNQ2 Epileptic Encephalopathy Due to a De Novo Variant and Review of the Literature. 一名两个月大的 KCNQ2 癫痫脑病婴儿因新发型变异导致的小脑发育不全和治疗过程及文献综述。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-15 DOI: 10.1002/ajmg.a.63909

Dilek Cebeci, Busranur Cavdarli, Pinar Ozbudak, Ebru Arhan, Kivilcim Gucuyener, Ercan Demir

{"title":"Cerebellar Hypoplasia and Treatment Course of a Two-Month-Old Infant With KCNQ2 Epileptic Encephalopathy Due to a De Novo Variant and Review of the Literature.","authors":"Dilek Cebeci, Busranur Cavdarli, Pinar Ozbudak, Ebru Arhan, Kivilcim Gucuyener, Ercan Demir","doi":"10.1002/ajmg.a.63909","DOIUrl":"https://doi.org/10.1002/ajmg.a.63909","url":null,"abstract":"In this paper, we report the treatment course, magnetic resonance imaging (MRI), and electroencephalography (EEG) findings of a two-month-old girl with KCNQ2 epileptic encephalopathy caused by a de novo variant. The patient started having seizures 2 days postnatally. Despite treatment with phenobarbital, phenytoin, levetiracetam, topiramate, clonazepam, vigabatrin, clobazam, and pyridoxine, she continued to have 10 or more seizures per day. EEG recordings showed multifocal epileptiform discharges with diffuse background slowing. MRI revealed left cerebellar hypoplasia. After lacosamide administration, the severity and frequency of seizures decreased by 80%. EEG recordings showed a significant improvement. A de novo heterozygous variant of c.1681C>A (p.Pro561Thr) in the KCNQ2 gene was detected. After carbamazepine add-on treatment, the patient achieved seizure-free status for about 2 years. This case demonstrates the efficacy of lacosamide against KCNQ2 epileptic encephalopathy. To our knowledge, this is the first report to document the association between cerebellar hypoplasia and KCNQ2 variants.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455911","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

Advancing Equity in Rare Disease Research: Insights From the Undiagnosed Disease Network. 促进罕见病研究的公平性：未确诊疾病网络的洞察力。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-14 DOI: 10.1002/ajmg.a.63904

Nicholas A Borja, Rory J Tinker, Stephanie A Bivona, Carson A Smith, Theodore Krijnse Locker, Samuela Fernandes, John A Phillips, Justin Stoler, Herman Taylor, Stephan Zuchner, Mustafa Tekin

{"title":"Advancing Equity in Rare Disease Research: Insights From the Undiagnosed Disease Network.","authors":"Nicholas A Borja, Rory J Tinker, Stephanie A Bivona, Carson A Smith, Theodore Krijnse Locker, Samuela Fernandes, John A Phillips, Justin Stoler, Herman Taylor, Stephan Zuchner, Mustafa Tekin","doi":"10.1002/ajmg.a.63904","DOIUrl":"10.1002/ajmg.a.63904","url":null,"abstract":"Rare diseases affect 6%-8% of the population and present diagnostic challenges, particularly for historically marginalized ethnic and racial groups. The Undiagnosed Diseases Network (UDN) aims to enhance diagnosis rates and research participation among such minoritized groups. A retrospective review was conducted from 2015 to 2023, analyzing 2235 UDN participants to evaluate its progress toward this objective. Data on demographics, disease phenotypes, diagnostic outcomes, and socioeconomic factors were collected and statistical analyses assessed differences among ethnic and racial groups. This demonstrated that Hispanic and Black non-Hispanic groups were underrepresented, while White non-Hispanic participants were overrepresented in the UDN compared to the US population. Individuals whose primary language was not English were also significantly underrepresented. Diagnosis rates varied, with the highest rates among Asian non-Hispanic (39.5%) and Hispanic (35.3%) groups and the lowest rate in the White non-Hispanic group (26.8%) (p < 0.001). Binomial logistic regression found, however, that only participant age and disease phenotype predicted the likelihood of receiving a diagnosis (p < 0.001). Persistent ethnic and racial disparities in UDN participation appear to be associated with major differences in application rates. Under-enrollment of historically marginalized ethnic and racial groups may be due to economic hardships and language barriers. No differences in the diagnostic yield among ethnic and racial groups were observed after controlling for other factors. This work highlights the value of comprehensive genetic evaluations for addressing healthcare disparities and suggests priorities for advancing inclusion in rare disease research.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455909","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