Case Reports in Genetics最新文献

A Novel LAMA5 Variant in Adult-Onset Focal Segmental Glomerulosclerosis: A Case Report. 成人发病局灶节段性肾小球硬化中一种新的LAMA5变异：1例报告。

Case Reports in Genetics Pub Date : 2026-10-18 eCollection Date: 2026-01-01 DOI: 10.1155/crig/7603821

Randah Abdullah Dahlan, Roaa Hani Fairoozy

{"title":"A Novel LAMA5 Variant in Adult-Onset Focal Segmental Glomerulosclerosis: A Case Report.","authors":"Randah Abdullah Dahlan, Roaa Hani Fairoozy","doi":"10.1155/crig/7603821","DOIUrl":"10.1155/crig/7603821","url":null,"abstract":"Focal segmental glomerulosclerosis (FSGS) is a common histopathological diagnosis among adult patients presenting with nephrotic syndrome. This pattern is associated with diverse underlying pathophysiological mechanisms, which may influence disease management, therapeutic response, and prognosis. Genetic forms of FSGS are caused by variants in genes encoding proteins expressed in podocytes or the glomerular basement membrane. Multiple genes have been implicated in the pathogenesis of genetic FSGS, and clinical presentation can vary depending on the specific gene involved. We report the case of a young man with nephrotic syndrome and a histopathological diagnosis of FSGS, in whom genetic testing identified a novel LAMA5 c.6940C > T p.(Arg2314Trp) variant in a consanguineous Saudi family, consistent with autosomal recessive inheritance. Family genetic analysis revealed that the proband's mother and two siblings are homozygous for the identified variant, whereas his father and the remaining two siblings are heterozygous. The variant is currently classified as a variant of uncertain significance (VUS). This report characterizes the associated clinical phenotype and discusses the findings of family segregation analysis in the context of variable expressivity and incomplete penetrance.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"7603821"},"PeriodicalIF":0.0,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prenatal Diagnosis and Individualized Perinatal Care in Apparently Nonmosaic Trisomy 9. 非镶嵌三体9的产前诊断和个体化围产期护理。

Case Reports in Genetics Pub Date : 2026-10-11 eCollection Date: 2026-01-01 DOI: 10.1155/crig/7719810

Hitoshi Isohata, Yoshihiro Yoshimura, Yu Yamazaki, Hiroyuki Goto, Kyoko Hattori, Takao Shimaoka, Fumio Takada, Daigo Ochiai

{"title":"Prenatal Diagnosis and Individualized Perinatal Care in Apparently Nonmosaic Trisomy 9.","authors":"Hitoshi Isohata, Yoshihiro Yoshimura, Yu Yamazaki, Hiroyuki Goto, Kyoko Hattori, Takao Shimaoka, Fumio Takada, Daigo Ochiai","doi":"10.1155/crig/7719810","DOIUrl":"https://doi.org/10.1155/crig/7719810","url":null,"abstract":"Background: Nonmosaic Trisomy 9 is a rare chromosomal abnormality, accounting for approximately 2.2%-2.7% of spontaneous abortions caused by autosomal trisomies, and is characterized by a heterogeneous multisystem phenotype and an extremely poor prognosis. Prenatal imaging may demonstrate severe multisystem abnormalities; however, these findings are not specific to Trisomy 9, making cytogenetic testing essential for definitive diagnosis. We report a case of prenatally diagnosed apparently nonmosaic Trisomy 9 in which diagnosis enabled individualized perinatal care.Case: A 44-year-old multiparous woman was referred to our hospital at 25 weeks' gestation because of severe fetal growth restriction and multiple structural anomalies. Amniocentesis at 28 weeks' gestation demonstrated 47,XY,+9 in all 100 examined colonies, consistent with apparently nonmosaic Trisomy 9. Following multidisciplinary counseling and shared decision-making, an individualized birth plan was developed. The family wished to avoid aggressive life-prolonging interventions while prioritizing the opportunity to meet their infant alive; therefore, fetal monitoring, cesarean delivery for fetal indications, and mask ventilation without further resuscitation were incorporated into the plan. Emergency cesarean delivery was performed at 36 weeks and 2 days for nonreassuring fetal status. The infant died approximately 9 h after birth while receiving family-centered palliative care.Conclusion: This case highlights the clinical importance of definitive prenatal cytogenetic diagnosis in apparently nonmosaic Trisomy 9, enabling phenotype-informed prognostic counseling and individualized perinatal management.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"7719810"},"PeriodicalIF":0.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exome Sequencing and MRI in Prenatal Diagnosis: A Case Report of Joubert Syndrome in Colombia. 外显子组测序和MRI产前诊断：哥伦比亚Joubert综合征1例报告。

Case Reports in Genetics Pub Date : 2026-09-23 eCollection Date: 2026-01-01 DOI: 10.1155/crig/7471200

Walter Annicchiarico, Leidy Ximena Peña-Pardo, Andrea Muñiz Redondo, Karla Fonseca Cruzate, Mauricio Castro, Gustavo Betin, Jezid Miranda

{"title":"Exome Sequencing and MRI in Prenatal Diagnosis: A Case Report of Joubert Syndrome in Colombia.","authors":"Walter Annicchiarico, Leidy Ximena Peña-Pardo, Andrea Muñiz Redondo, Karla Fonseca Cruzate, Mauricio Castro, Gustavo Betin, Jezid Miranda","doi":"10.1155/crig/7471200","DOIUrl":"10.1155/crig/7471200","url":null,"abstract":"Objective: To report the prenatal diagnosis of CSPP1-related Joubert Syndrome 21 (JS21) in a fetus with multiple congenital anomalies, highlighting the complementary role of detailed neuroimaging and molecular genetic testing.Methods: A fetus with suspected central nervous system anomalies underwent detailed prenatal ultrasound and fetal neurosonography, followed by magnetic resonance imaging (MRI) and exome sequencing. We reviewed prenatal imaging, molecular findings, and postnatal outcomes.Results: A 25-year-old G4P2011 patient with a history of adverse pregnancy outcomes associated with fetal malformations was referred at 32 weeks of gestation. Ultrasound findings included occipital meningocele, cerebellar vermis agenesis, and bilateral cleft lip and palate. Fetal MRI confirmed the characteristic molar tooth sign, raising suspicion of Joubert syndrome. Exome sequencing identified a homozygous canonical splice-site variant in CSPP1, NM_001382391.1:c.2968 + 1G > A (rs587777142), classified as pathogenic according to ACMG/AMP criteria. The pregnancy resulted in the birth of a female neonate weighing 3165 g, and postnatal clinical and imaging evaluation supported the prenatal diagnosis of CSPP1-related JS21.Conclusions: This case illustrates the value of integrating detailed fetal neuroimaging with molecular genetic testing for the prenatal diagnosis of Joubert syndrome. Recognition of characteristic imaging findings can guide targeted interpretation of genetic results, allowing earlier diagnosis, more accurate counseling, and coordinated prenatal and postnatal care.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"7471200"},"PeriodicalIF":0.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GRIA3 Duplication at Xq25 in a Young Adult Male With Profound Intellectual Disability and Morbid Obesity: A Case Report. 严重智力残疾和病态肥胖的年轻成年男性中Xq25的GRIA3重复：1例报告

Case Reports in Genetics Pub Date : 2026-09-22 eCollection Date: 2026-01-01 DOI: 10.1155/crig/7670059

Shuichi Yatsuga

{"title":"GRIA3 Duplication at Xq25 in a Young Adult Male With Profound Intellectual Disability and Morbid Obesity: A Case Report.","authors":"Shuichi Yatsuga","doi":"10.1155/crig/7670059","DOIUrl":"10.1155/crig/7670059","url":null,"abstract":"We report a 22-year-old Japanese male with profound intellectual disability (IQ 16), autism spectrum disorder (ASD), and drug-controlled epilepsy referred for obesity management (height 182.7 cm, weight 139.7 kg, and BMI 41.9 kg/m2). Clinical features included brachycephaly, deep-set eyes, prominent supraorbital ridges, bitemporal narrowing, broad nasal root, hypotonia, hyporeflexia, and sleep-wake cycle disorder. Chromosomal microarray analysis (CMA) performed by SRL Inc. (Tokyo, Japan) using an Affymetrix-based platform (specific array model not disclosed by the laboratory) identified a duplication at Xq25 (minimum interval: chrX:121,515,588-122,689,238; maximum interval: chrX:121,468,613-122,733,639; GRCh37/hg19; arr[GRCh37] Xq25 (121,515,588_122,689,238) × 2) encompassing the entire GRIA3 gene, classified as a variant of uncertain significance (VUS). The duplicated interval did not encompass STAG2. Parental genetic testing was declined and exome or genome sequencing was not performed; an alternative molecular diagnosis cannot be excluded. Comorbid findings included Grade 2 hypertension (161/99 mmHg), hemoglobin elevation (17.2 g/dL) possibly consistent with sleep-disordered breathing (not formally evaluated), hepatic steatosis on ultrasonography, splenomegaly, and hyperuricemia. Progressive weight gain had begun at approximately 9 years of age, preceding antipsychotic and antiepileptic polypharmacy by approximately 8 years. Dietary and physical activity guidance without pharmacotherapy resulted in an approximately 4-kg weight reduction over 4 months (BMI 40.6 kg/m2). This case describes a range of metabolic findings in a patient carrying a GRIA3 duplication.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"7670059"},"PeriodicalIF":0.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149026217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expanding the Progeroid Laminopathy Spectrum: Clinical Variability and Later-Onset Phenotype in Homozygous LMNA c.1579C>T (p.Arg527Cys) Associated Mandibuloacral Dysplasia. 扩大早老年性椎板病谱系：纯合子LMNA c.1579C>T （p.Arg527Cys）相关下颌髁突发育不良的临床变异性和后发表型。

Case Reports in Genetics Pub Date : 2026-09-19 eCollection Date: 2026-01-01 DOI: 10.1155/crig/5579887

Eszter Sara Arany, David Zocche, Jan Cobben

引用次数: 0

ZTTK Syndrome Expanding the Cardiac Phenotype: A Case of Shone's Complex With a Novel SON Variant and Focused Review of the Cardiac Manifestations in ZTTK Syndrome. ZTTK综合征扩大心脏表型：一种新型SON变异的Shone复合体病例及ZTTK综合征心脏表现的重点综述

Case Reports in Genetics Pub Date : 2026-09-16 eCollection Date: 2026-01-01 DOI: 10.1155/crig/3473063

John Coleman, Abdul L Shakerdi, Veronika Dvorakova, Janna Kenny

{"title":"ZTTK Syndrome Expanding the Cardiac Phenotype: A Case of Shone's Complex With a Novel SON Variant and Focused Review of the Cardiac Manifestations in ZTTK Syndrome.","authors":"John Coleman, Abdul L Shakerdi, Veronika Dvorakova, Janna Kenny","doi":"10.1155/crig/3473063","DOIUrl":"10.1155/crig/3473063","url":null,"abstract":"Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome is a rare multisystem neurodevelopmental disorder caused by heterozygous variants in SON. Presented here is a case of a four-year-old female with multiple rare manifestations including a complex neurodevelopmental disorder, Shone complex and a simple capillary malformation. Genetic analysis confirmed a novel frameshift variant in SON, which was classified as pathogenic. The patient has epilepsy and moderate-to-severe global developmental delay. Her epilepsy is well controlled with levetiracetam monotherapy. A focused literature review was undertaken and found that cardiac defects are reported in an estimated 22% of cases to date. Obstructive left-sided heart lesions are rarely reported, and this is the first reported case of Shone complex in the reported ZTTK patient cohorts. Loss-of-function variants in SON are implicated in abnormal RNA expression and splicing in genes involved in neural migration and metabolism. The literature review did not reveal an increased association between epilepsy in ZTTK patients and that in congenital heart disease compared with ZTTK patients without congenital heart disease, supporting the previous findings that SON is likely to be involved in multiple critical biological processes. Mitochondrial dysfunction was implicated in previous reports of loss-of-function SON variants and supported by the cardiac phenotype in previously reported cases.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"3473063"},"PeriodicalIF":0.0,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13583451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Novel Pathogenic Frameshift Variant Associated With Holt-Oram Syndrome: A Case Report. 一种与Holt-Oram综合征相关的新型致病移码变异：一例报告。

Case Reports in Genetics Pub Date : 2026-09-16 eCollection Date: 2026-01-01 DOI: 10.1155/crig/8875290

Soyi Sarkar, Akshay N Rana, Garrett Gianneschi, Peyman Bizargity

引用次数: 0

A Case Report of a Novel Myelin Protein Zero (MPZ) Pathogenic Variant in Charcot-Marie-Tooth Disease Combined With Type 2 Diabetes. 一种新的髓鞘蛋白零（MPZ）致病变异在腓骨-玛丽-牙病合并2型糖尿病中的病例报告。

Case Reports in Genetics Pub Date : 2026-09-12 eCollection Date: 2026-01-01 DOI: 10.1155/crig/8838487

Lu Xia, Liyan Cai, Xin Chen, Kun Zhou, Wei Huang, Yuanyuan Zhu, Shinian Yang

{"title":"A Case Report of a Novel Myelin Protein Zero (MPZ) Pathogenic Variant in Charcot-Marie-Tooth Disease Combined With Type 2 Diabetes.","authors":"Lu Xia, Liyan Cai, Xin Chen, Kun Zhou, Wei Huang, Yuanyuan Zhu, Shinian Yang","doi":"10.1155/crig/8838487","DOIUrl":"10.1155/crig/8838487","url":null,"abstract":"Charcot-Marie-Tooth (CMT) disease is the collective term for the most common inherited peripheral neuropathies, affecting both motor and sensory nerves. A typical CMT patient presents with slowly progressive distal muscle weakness and atrophy that primarily involves the small foot muscles, peroneal muscles, and, often later, the muscles of the hands and forearms. Foot deformities, most commonly pes cavus and claw toes, are common and can lead to gait impairments. In this paper, we report a patient with an intermediate CMT (CMT-Int) type carrying a novel pathogenic variant in the MPZ gene combined with type 2 diabetes. The patient's initial symptoms included a gradual onset of muscle wasting, weakness, and sensory impairment in the lower limbs. Electrophysiological findings suggested widespread peripheral nerve damage affecting both sensory and motor fibers, with a predominant demyelinating pattern accompanied by axonal damage. Genetic testing identified a previously unreported heterozygous mutation in the MPZ gene, specifically c.548G > A, p.Trp183∗. This alteration results in the replacement of the 183rd amino acid (tryptophan) by a stop codon. This premature stop codon is predicted to escape nonsense-mediated mRNA decay, resulting in a C-terminally truncated protein that may exert a dominant-negative effect. Although a different variant affecting the same codon (c.549G > A, p.Trp183∗, VCV000917145.1) has been documented, this particular pathogenic mutation has not been previously recorded. After being diagnosed with CMT, the patient developed type 2 diabetes following pancreatic cyst surgery in September 2022. The presence of both conditions exposed her peripheral nerves to congenital structural abnormalities combined with the metabolic consequences of chronic hyperglycemia and local ischemia, thereby exacerbating nerve injury.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"8838487"},"PeriodicalIF":0.0,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 Cases of ASXL3-Related Bainbridge-Ropers Syndrome: Clinical and Genetic Evaluation. 2例asxl3相关Bainbridge-Ropers综合征：临床和遗传评价。

Case Reports in Genetics Pub Date : 2026-09-03 eCollection Date: 2026-01-01 DOI: 10.1155/crig/9304690

Şirin Sedef Baş, Burcu Yeter, Nursel H Elcioglu

{"title":"Two Cases of ASXL3-Related Bainbridge-Ropers Syndrome: Clinical and Genetic Evaluation.","authors":"Şirin Sedef Baş, Burcu Yeter, Nursel H Elcioglu","doi":"10.1155/crig/9304690","DOIUrl":"10.1155/crig/9304690","url":null,"abstract":"ASXL3-related disorder, also known as Bainbridge-Ropers syndrome (BRPS), is a neurodevelopmental condition first described by Bainbridge et al. and characterized by delayed psychomotor development, learning difficulties, characteristic craniofacial features, hypotonia, behavioral problems, and feeding problems. It is associated with heterozygous truncating pathogenic variants in the ASXL3 gene, located at chromosomal region 18q12.1. In this study, exome sequencing was performed in a 7-month-old male and a 4-year-old female patient who presented with unexplained developmental delay. De novo truncating variants in the ASXL3 gene were identified in both patients. Genetic analysis revealed that Patient 1 had a canonical splice-site likely pathogenic variant in the ASXL3 gene c.3039 + 1G > A. Patient 2 had a pathogenic variant in the ASXL3 gene c.1864_1867dup; p.Thr623Metfs∗25. We compared the patients' physical examination findings, clinical characteristics, and genetic results with those reported in the literature. This case report emphasizes the phenotypic spectrum of this disorder and describes a variant that, to our knowledge, has not been previously reported in the literature.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2026 ","pages":"9304690"},"PeriodicalIF":0.0,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Rare Finding of Mosaic 45,XX,der(13;21)(q10;q10)[15]/46,XX,r(13)(p11.2q33) Following Abnormal Prenatal Chromosomal Microarray Testing. 产前异常染色体芯片检测罕见发现马赛克45，XX,der(13;21)(q10;q10)[15]/46，XX,r(13)（p11.2q33）。

Case Reports in Genetics Pub Date : 2026-08-31 eCollection Date: 2026-01-01 DOI: 10.1155/crig/7026115

Katherine M Haines, Deborah M Hazard, Billie Carstens, Peter M Brzeskiewicz, Thomas M Gilfillan, Hala Nijmeh, Chandra Perez-Gill, Mikayla Stoecker, Farrah Rajabi, Mary M Haag, Stephen J Wicks

引用次数: 0