American Journal of Medical Genetics Part A最新文献_第4页

Elective Terminations Because of Fetal Abnormalities: Findings in A Tertiary Maternity Center Over 41 Years (1972-2012). 因胎儿异常而选择性终止妊娠：在一家三级产科中心超过41年（1972-2012）的调查结果。

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.64051

Lewis B Holmes, Hamzeh Nasri, Anne-Therese Hunt, Hanah Z Nasri

{"title":"Elective Terminations Because of Fetal Abnormalities: Findings in A Tertiary Maternity Center Over 41 Years (1972-2012).","authors":"Lewis B Holmes, Hamzeh Nasri, Anne-Therese Hunt, Hanah Z Nasri","doi":"10.1002/ajmg.a.64051","DOIUrl":"https://doi.org/10.1002/ajmg.a.64051","url":null,"abstract":"Finding abnormalities in a fetus by prenatal testing during pregnancy is a common reason why parents choose to terminate a pregnancy. A malformations surveillance program of all births at a tertiary center in Boston was used to identify each elective termination because of a malformation detected prenatally. A severity scale of malformations was used: lethal (anencephaly), severe-handicapping (Down syndrome; myelomeningocele), moderate-fixable (omphalocele) and mild (postaxial polydactyly, type B). Demographic characteristics and the findings in prenatal testing were recorded. Six hundred and sixty-nine elective terminations because of fetal abnormalities were identified. A destructive procedure (dilation and evacuation; D&E) was the primary method used to end the pregnancy. The gestational age at the time of termination was 18 to 19 weeks. The two most common sequences of events were: (1) imaging by ultrasound established the diagnosis; (2) imaging by ultrasound led to amniocentesis which established the diagnosis. Ninety-four percent of the abnormalities were either lethal or severe-handicapping. The discovery of a fetal abnormality was a surprise to 98% of the parents. Single women differed from married women in being younger, less well-educated, less likely to have health insurance, and more likely to terminate a pregnancy with moderate-fixable malformations.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64051"},"PeriodicalIF":1.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959658","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 Case of Penttinen Syndrome With Radiographic Acroosteolysis From Age 3 Years. 3岁时Penttinen综合征并发肢端骨溶解症1例。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-04-18 DOI: 10.1002/ajmg.a.64088

Kazuhiro Shimura, Machiko Toki, Yuko Tsujioka, Gen Nishimura, Tomohiro Ishii, Tomonobu Hasegawa

{"title":"A Case of Penttinen Syndrome With Radiographic Acroosteolysis From Age 3 Years.","authors":"Kazuhiro Shimura, Machiko Toki, Yuko Tsujioka, Gen Nishimura, Tomohiro Ishii, Tomonobu Hasegawa","doi":"10.1002/ajmg.a.64088","DOIUrl":"https://doi.org/10.1002/ajmg.a.64088","url":null,"abstract":"Premature aging syndrome, Penttinen type (Penttinen syndrome) is a progeroid syndrome with facial alterations (thin hair and progressive recession of the maxillozygomatic bones with pseudoprognathism), skin abnormalities (scleroderma with epidermal and dermal atrophy, lipoatrophy, chronic ulcers, and keloid-like hypertrophic lesions), corneal changes (vascularization and opacity), cerebral vascular anomalies, and acroosteolysis. This syndrome is caused by heterozygous, gain-of-function pathogenic variants in the PDGFRB gene. Only 10 affected individuals have been reported to date, and thus the phenotypic spectrum of the disorder, particularly in early childhood, remains elusive. We reported here the clinical course of an affected male from early childhood to young adulthood. Thin limbs and short fingers attracted medical attention at age 3 years, at which time he had already developed maxillary hypoplasia, keloids, and acroosteolysis, all of which progressively worsened with age. Joint contractures and scoliosis became apparent during adolescence. Progressive maxillary recession and scleroderma remarkably altered his facial gestalt over time, including the development of exophthalmos, small auricles, short philtrum, and small mouth. Sanger sequencing identified a recurrent, de novo pathogenic variant in the PDGFRB gene (c.1994T > C, p.Val665Ala). This report on the clinical course through childhood provides additional insight into the natural history of Penttinen syndrome.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64088"},"PeriodicalIF":1.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959031","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 "Exome Sequencing Detects Uniparental Disomy of Chromosome 4 Revealing a LARP7 Pathogenic Variant Responsible for Alazami Syndrome: A Case Report". 更正“外显子组测序检测到4号染色体的单亲二体，揭示了导致阿拉扎米综合征的LARP7致病变异：一个病例报告”。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-04-17 DOI: 10.1002/ajmg.a.64082

引用次数: 0

Compound Heterozygous Variants in ZSWIM7 Gene Linked to Infertility and Its Role in Gonadal Development. 与不育相关的ZSWIM7基因复合杂合变异体及其在性腺发育中的作用

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-04-17 DOI: 10.1002/ajmg.a.64078

Denise M Christofolini, Guilherme Pinn, Thainá Vilella, Maria I Melaragno, Mariana Moysés-Oliveira, Luciano Pompei, Bianca Bianco, Caio P Barbosa

{"title":"Compound Heterozygous Variants in ZSWIM7 Gene Linked to Infertility and Its Role in Gonadal Development.","authors":"Denise M Christofolini, Guilherme Pinn, Thainá Vilella, Maria I Melaragno, Mariana Moysés-Oliveira, Luciano Pompei, Bianca Bianco, Caio P Barbosa","doi":"10.1002/ajmg.a.64078","DOIUrl":"https://doi.org/10.1002/ajmg.a.64078","url":null,"abstract":"This study aims to elucidate the role of the ZSWIM7 gene in the etiology of infertility, focusing on its potential association with premature ovarian insufficiency and azoospermia. We investigated an 18-year-old female patient who presented with primary amenorrhea, hypoplasia of the uterus and ovaries, Tanner stage II breast and pubic hair development, severe scoliosis (surgically repaired), recurrent urinary infections, and hypothyroidism. Genetic analysis revealed two heterozygous variants: a loss-of-function frameshift mutation in ZSWIM7 and a chromosomal deletion encompassing the same gene-a combination not previously described in the literature. Diagnostic techniques included G-banding karyotype analysis, evaluation of FMR1 premutation by PCR, and whole-genome sequencing to identify gene variants and copy number variations (CNVs). The patient carries a pathogenic single-nucleotide variant (SNV) and, in the other chromosome, a deletion encompassing the ZSWIM7 gene. In silico network analysis indicated that ZSWIM7 interacts with genes involved in DNA repair and gonadal development. A literature review identified previous cases of homozygosity for the same variant, but this is the first reported case of compound heterozygosity involving both a base deletion and a CNV. A review of five prior studies on ZSWIM7 variants and infertility supports the conclusion that ZSWIM7 is associated with infertility in both sexes. Our findings suggest that loss-of-function pathogenic variants in ZSWIM7 negatively affect the formation and maintenance of male and female gonads.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64078"},"PeriodicalIF":1.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970811","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 Rare Cause of Primary Microcephaly: 4 New Variants in CDK5RAP2 Gene and Review of the Literature. 原发性小头症的罕见病因：CDK5RAP2基因的4个新变异及文献综述。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-04-17 DOI: 10.1002/ajmg.a.64072

Murat Erdogan, Aysel Unal, Muhammet Ensar Dogan, Sumeyra Oguz, Burhan Balta, Yasin Ada, Aslıhan Kiraz, Munis Dundar

{"title":"A Rare Cause of Primary Microcephaly: 4 New Variants in CDK5RAP2 Gene and Review of the Literature.","authors":"Murat Erdogan, Aysel Unal, Muhammet Ensar Dogan, Sumeyra Oguz, Burhan Balta, Yasin Ada, Aslıhan Kiraz, Munis Dundar","doi":"10.1002/ajmg.a.64072","DOIUrl":"https://doi.org/10.1002/ajmg.a.64072","url":null,"abstract":"Autosomal recessive primary microcephaly (MCPH) is a rare, genetically heterogeneous disorder characterized by congenital microcephaly, non-progressive intellectual disability, and absence of neurological abnormalities. Pathogenic variants in CDK5RAP2, linked to MCPH3, represent one of the least common causes of MCPH. Autosomal recessive primary microcephaly (MCPH) is a rare, genetically heterogeneous disorder characterized by reduced head size at birth, variable intellectual disability, and no neurological abnormalities. Among This study aimed to identify and characterize novel genetic and clinical findings in patients with CDK5RAP2 gene variants, contributing to the understanding of this rare disorder. Whole exome sequencing (WES) was conducted in 11 patients from five consanguineous families. Six CDK5RAP2 variants were identified, four of which were novel (c.4421del, c.1968G>C, c.3460C>T, c.625dup). Ten patients harbored homozygous variants, whereas one displayed compound heterozygosity. Segregation analysis confirmed carrier status in parents. Clinical evaluations aligned with typical MCPH3 features, though phenotypic variability was observed. This study expands the CDK5RAP2 variant spectrum and reinforces WES as a critical tool for diagnosing rare MCPH subtypes, guiding carrier screening, and improving genetic counseling. The novel variants highlight the genetic diversity underlying MCPH3, urging broader genomic investigations in undiagnosed cases.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64072"},"PeriodicalIF":1.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962860","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

Dentofacial Findings and Management of two Pediatric Patients With Bainbridge-Ropers Syndrome: A Case Report. 2例小儿Bainbridge-Ropers综合征的牙面表现和治疗：1例报告。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-04-16 DOI: 10.1002/ajmg.a.64090

Aslı Aşık, Ezgi Cansu Fırıncıoğulları, Enise Avcı Durmuşalioğlu, Dilşah Çoğulu, Tahir Atik, Aslıhan Mediha Erdinç, Ozgur Cogulu

{"title":"Dentofacial Findings and Management of two Pediatric Patients With Bainbridge-Ropers Syndrome: A Case Report.","authors":"Aslı Aşık, Ezgi Cansu Fırıncıoğulları, Enise Avcı Durmuşalioğlu, Dilşah Çoğulu, Tahir Atik, Aslıhan Mediha Erdinç, Ozgur Cogulu","doi":"10.1002/ajmg.a.64090","DOIUrl":"https://doi.org/10.1002/ajmg.a.64090","url":null,"abstract":"Bainbridge-Ropers Syndrome(BPRS) is a rare autosomal dominant genetic disorder resulting from heterozygous mutations in the ASXL3(Additional Sex Comb-Like 3) gene located on chromosome 18q12. To date, only 45 cases have been documented in the literature. BPRS is characterized by a range of clinical features, including feeding difficulties, hypotonia, distinctive dysmorphic facial features, high-arched palate, and intellectual disability. This case report aims to present two pediatric patients diagnosed with BPRS, emphasize newly identified oro-dental manifestations, and propose a comprehensive dental management plan. In Case #1, a 10-year-old female patient presented to the clinic with concerns of developmental delay and spinal deformity. Physical examination revealed trigonocephaly, thoracic kyphosis, strabismus, hirsutism, bitemporal narrowing, and bilateral coxa valga. Additionally, the patient exhibited failure to thrive, language difficulties, and mild intellectual disability. Oral examination identified a high-arched palate, fibrotic frenulum, narrow maxilla, and posterior crossbite. In Case #2, a 6-year-old female patient presented with developmental delay, language difficulties, and mouth breathing. Physical findings included trigonocephaly, bitemporal narrowing, strabismus, hirsutism, and arched eyebrows. Oral examination revealed a high-arched palate, narrow maxilla, and open bite. For both cases, preventive dental interventions were implemented, including the application of fissure sealants, fluoride varnishes, dietary regulation, and the use of interceptive orthodontic appliances. Children diagnosed with BPRS require ongoing medical and dental management through a multidisciplinary approach to address the complex and varied manifestations of the disorder effectively.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64090"},"PeriodicalIF":1.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963909","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 Case of Prader-Willi Syndrome With a Deletion Including MAGEL2, NDN, and MKRN3, but Excluding SNRPN and SNORD116. praper - willi综合征1例，缺失包括MAGEL2、NDN和MKRN3，但不包括SNRPN和SNORD116。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-04-15 DOI: 10.1002/ajmg.a.64070

Jannis Buecking, Yu An, Weimin Bi, Katrin Hinderhofer, Susanne Theiß, Anne Slavotinek, Christian P Schaaf

{"title":"A Case of Prader-Willi Syndrome With a Deletion Including MAGEL2, NDN, and MKRN3, but Excluding SNRPN and SNORD116.","authors":"Jannis Buecking, Yu An, Weimin Bi, Katrin Hinderhofer, Susanne Theiß, Anne Slavotinek, Christian P Schaaf","doi":"10.1002/ajmg.a.64070","DOIUrl":"https://doi.org/10.1002/ajmg.a.64070","url":null,"abstract":"Prader-Willi syndrome (PWS) is a neurodevelopmental disorder typically caused by large deletions or imprinting defects on chromosome 15q11.2, encompassing multiple genes. While the contribution of individual genes to the PWS phenotype remains unclear, previous studies suggested that isolated deletions of MAGEL2, NDN, and MKRN3, excluding the SNRPN/SNORD116 locus, were insufficient to cause PWS. Here, we present a case report of a patient with an isolated deletion of MAGEL2, NDN, and MKRN3 who exhibits the full PWS phenotype, including neonatal hypotonia, developmental delay, hyperphagia, obesity, and behavioral issues. We explore the potential mechanisms underlying this case and investigate the potential contribution of the deleted genes to the observed phenotype. This case challenges previous findings and highlights the complexity of genotype-phenotype correlations in PWS. We compare the clinical data of our patient with previous reports and discuss the discrepancy with earlier findings. Our findings underscore the need for further research to fully elucidate the roles of individual genes within the PWS locus and the mechanisms underlying the phenotypic spectrum of this complex disorder.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64070"},"PeriodicalIF":1.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956115","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

Hypersensitivity Reaction and a Single-Bag Rapid Desensitization to Idursulfase. 对伊杜硫酶的超敏反应和单袋快速脱敏。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-04-12 DOI: 10.1002/ajmg.a.64089

Jenna H Jung, Berrin Monteleone, Meghan McGath, Blanka Kaplan

引用次数: 0

Biallelic Variant, c.644-13_644-9del in UNC50 Is Associated With Congenital Myasthenia Syndrome. UNC50双等位基因c.644-13_644-9del与先天性肌无力综合征相关

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-04-12 DOI: 10.1002/ajmg.a.64086

Mangalore S Shravya, Greeshma Purushothama, Periyasamy Radhakrishnan, Malavika Hebbar, Shyamala Guruvare, Mary Mathew, Gandham SriLakshmi Bhavani, Shruti Bajaj, Katta M Girisha, Anju Shukla, Shalini S Nayak

{"title":"Biallelic Variant, c.644-13_644-9del in UNC50 Is Associated With Congenital Myasthenia Syndrome.","authors":"Mangalore S Shravya, Greeshma Purushothama, Periyasamy Radhakrishnan, Malavika Hebbar, Shyamala Guruvare, Mary Mathew, Gandham SriLakshmi Bhavani, Shruti Bajaj, Katta M Girisha, Anju Shukla, Shalini S Nayak","doi":"10.1002/ajmg.a.64086","DOIUrl":"https://doi.org/10.1002/ajmg.a.64086","url":null,"abstract":"UNC50 encodes a transmembrane protein that plays a crucial role in L-acetylcholine receptor trafficking and thus cholinergic transmission at the neuromuscular junction. Previously, a biallelic loss-of-function variant in UNC50 was reported in an individual with lethal arthrogryposis multiplex congenita. We herein describe affected individuals from two unrelated families with arthrogryposis multiplex congenita in one family and a severe early-onset neuromuscular dysfunction in the other, both within the spectrum of congenital myasthenia syndrome. A biallelic variant, c.644-13_644-9del, p.? in intron 5 of UNC50 (NM_014044.7) was identified in both families. Transcript analysis in the peripheral blood cDNA of the heterozygous carrier parents of family 1 revealed that the c.644-13_644-9del variant leads to aberrant splicing. With these findings, we validated the association of disease-causing variants in UNC50 with congenital myasthenia syndrome.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64086"},"PeriodicalIF":1.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953804","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

TYMS-ENOSF1 Dyskeratosis Congenita in a Patient With Ring Chromosome 18: A Case Report. 18号环染色体TYMS-ENOSF1先天性角化不良1例报告。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-04-10 DOI: 10.1002/ajmg.a.64081

Rayad B Shams, Elizabeth L Nieman, Yezmin Perilla-Young, Dean S Morrell, Clara Hildebrandt

引用次数: 0