Clinical Genetics最新文献_第7页

Six New Cases of 22q13.2 Gain Including TFC20: First Report of Triplication and Smallest Duplication Associated With Neurodevelopmental Delays. 包括TFC20在内的6例22q13.2新增病例：首次报道与神经发育迟缓相关的三次重复和最小重复

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-06-30 DOI: 10.1111/cge.14781

Etienne Bizot, Dima Jouni, Caroline Rooryck, Juliet Taylor, Marine Legendre, Lorelei Charbonnier, Julia Metreau, Emmanuelle Benaloun, Audrey Pinson, Geneviève Quenum, Jérôme Bouligand, Gérard Tachdjian, Philippe Labrune, Lucie Tosca

{"title":"Six New Cases of 22q13.2 Gain Including TFC20: First Report of Triplication and Smallest Duplication Associated With Neurodevelopmental Delays.","authors":"Etienne Bizot, Dima Jouni, Caroline Rooryck, Juliet Taylor, Marine Legendre, Lorelei Charbonnier, Julia Metreau, Emmanuelle Benaloun, Audrey Pinson, Geneviève Quenum, Jérôme Bouligand, Gérard Tachdjian, Philippe Labrune, Lucie Tosca","doi":"10.1111/cge.14781","DOIUrl":"https://doi.org/10.1111/cge.14781","url":null,"abstract":"To date, only one study describes three unrelated cases of neurodevelopmental disorders associated with duplications in 22q13.2, which include the TCF20 gene. In contrast, TCF20 variants and deletions are well characterized. Here, we report six new cases of 22q13.2 gain, including TCF20, identified through array-comparative genomic hybridization (array-CGH). Probands exhibited neurodevelopmental delay, and several presented with facial dysmorphism, abnormal growth parameters, and abnormalities affecting the skeletal, respiratory, genitourinary, and/or cardiovascular systems. We documented one 440 Kb triplication and five cases of duplication ranging from 82.5 Kb to 3.03 Mb in size. Co-segregation analysis of the CNV and clinical symptoms supports variable expressivity. However, the complete penetrance of these gains remains questionable compared to the known pathogenic variants and structural variations associated with loss of function. We discuss the genotype-phenotype correlations and hypotheses surrounding the impairment of TCF20 protein function.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","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 Genetic and Phenotypic Spectrum of POLRMT-Related Mitochondrial Disease. 扩大polrmt相关线粒体疾病的遗传和表型谱。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-06-29 DOI: 10.1111/cge.70011

Mahmoud R Fassad, Sebastian Valenzuela, Monika Oláhová, Jack J Collier, Charlotte V Y Knowles, Eleni Mavraki, Miriam Elbracht, Nergis Güzel, Thomas Herberhold, Ingo Kurth, Andrea Maier, Larissa Mattern, Carol Saunders, Helen McCullagh, Katrin Õunap, Saskia B Wortmann, Andre Reis, Lei Zhang, Claes M Gustafsson, Robert McFarland, Robert W Taylor

引用次数: 0

Further Exploring the TRRAP Genotype-Phenotype Correlations: Report of Three New Patients With A Focus on Skeletal Anomalies. 进一步探索TRRAP基因型-表型相关性：三例以骨骼异常为重点的新患者报告。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-06-29 DOI: 10.1111/cge.70013

Chiara Minotti, Sara Terreri, Andrea Del Fattore, Francesca Romana Lepri, Rosario Ruta, Maria Iascone, Laura Pezzoli, Maria Lisa Dentici, Antonio Novelli, Michelina Armando, Daniela Longo, Giuseppe Novelli, Domenico Barbuti, Andrea Bartuli, Ugo Cavallari, Ludovico Graziani, Maria Cristina Digilio, Lorenzo Sinibaldi

{"title":"Further Exploring the TRRAP Genotype-Phenotype Correlations: Report of Three New Patients With A Focus on Skeletal Anomalies.","authors":"Chiara Minotti, Sara Terreri, Andrea Del Fattore, Francesca Romana Lepri, Rosario Ruta, Maria Iascone, Laura Pezzoli, Maria Lisa Dentici, Antonio Novelli, Michelina Armando, Daniela Longo, Giuseppe Novelli, Domenico Barbuti, Andrea Bartuli, Ugo Cavallari, Ludovico Graziani, Maria Cristina Digilio, Lorenzo Sinibaldi","doi":"10.1111/cge.70013","DOIUrl":"https://doi.org/10.1111/cge.70013","url":null,"abstract":"TRRAP encodes a multidomain pseudokinase involved in histone acetyltransferase complexes. TRRAP pathogenic variants were linked to neurodevelopmental disorders, intellectual disability, congenital anomalies, and hearing loss. We report on three unrelated patients with TRRAP missense variants. Patient #1, a girl with severe intellectual disability, autism features, and preaxial polydactyly, displays the c.5575C>T, p.(Arg1859Cys) variant. Patient #2, a boy with developmental delay and facial anomalies, harbors the c.5647G>A, p.(Gly1883Arg) variant. Patient #3, a girl with developmental delay, epilepsy, and renal artery stenosis, carries the c.8572C>T, p.(Arg2858Trp) variant. These new cases broaden the TRRAP phenotypic spectrum, updating genotype-phenotype correlations. Osteoclast differentiation in Patient #1 and TRRAP expression in osteoclasts and osteoblasts were analyzed, leading to the assumption of a role of TRRAP in bone remodeling and in the observed skeletal anomalies.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PMS2 c.2117del (p.Lys706Serfs*19) is the Most Frequent Cancer-Associated Founder Pathogenic Variant in the French-Canadian Population of Quebec, Canada. PMS2 c.2117del （p.Lys706Serfs*19）是加拿大魁北克法裔加拿大人群中最常见的癌症相关始发致病变异。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-06-23 DOI: 10.1111/cge.14784

Anne-Laure Chong, Alejandro Mejia-Garcia, Supriya Behl, Zaki El Haffaf, Sébastien Chénier, Bruno Maranda, Valérie Désilets, Sébastien Lévesque, Lysanne Castonguay, Anne-Marie Mes-Masson, Sylvie Giroux, François Rousseau, Nancy Hamel, George Chong, Simon Gravel, William D Foulkes

{"title":"PMS2 c.2117del (p.Lys706Serfs*19) is the Most Frequent Cancer-Associated Founder Pathogenic Variant in the French-Canadian Population of Quebec, Canada.","authors":"Anne-Laure Chong, Alejandro Mejia-Garcia, Supriya Behl, Zaki El Haffaf, Sébastien Chénier, Bruno Maranda, Valérie Désilets, Sébastien Lévesque, Lysanne Castonguay, Anne-Marie Mes-Masson, Sylvie Giroux, François Rousseau, Nancy Hamel, George Chong, Simon Gravel, William D Foulkes","doi":"10.1111/cge.14784","DOIUrl":"10.1111/cge.14784","url":null,"abstract":"We identified a PMS2 variant (NM_000535.7:c.2117del, p.Lys706Serfs*19) in 22 French-Canadian (FC) families from Quebec with Lynch syndrome (LS; n = 21) or constitutional mismatch repair deficiency (CMMRD; n = 1). We aimed to (a) confirm its founder origin, (b) assess its allele frequency in the FC population, and (c) determine its contribution to the risk of developing various cancers in this population. We identified a haplotype common to all c.2117del alleles spanning 666 kb to 1.37 Mb, confirming the founder nature of the variant. In affected cases, the variant was found in 0 out of 821 breast cancer cases, 8 out of 693 (1.15%) endometrial cancer (EC) cases, and 1 out of 191 (0.52%) colorectal cancer (CRC) cases. In unaffected persons, the variant was identified in 22/6347 newborns (0.35%) and in 21/18129 FC CARTaGENE cohort participants (0.12%). Within this cohort, an excess of CRC (odds ratio: 10.7; 95% CI: 1.42-80.1; p value = 0.022), but not EC, was seen among heterozygotes for the PMS2 founder variant. Analysis of the variant in 24 subregions of Quebec showed over-representation in 5 of them. Here, we report the most frequent genetic cause of mismatch repair deficiency syndromes identified thus far in the FC population of Quebec.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unraveling the Role of WDR91: Case Report of a Previously Unrecognized Clinical Entity. 揭示WDR91的作用：一个以前未被认识的临床实体的病例报告。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-06-23 DOI: 10.1111/cge.70012

Nikolaos M Marinakis, Afrodite Kampouraki, Danai Veltra, Faidon-Nikolaos Tilemis, Maria Vasilopoulou, Aikaterini Dokou, Elissavet Georgiadou, Euthalia Karavergou, Maria Christolouka, Alexis Alexopoulos, Dimitra Kirillidi, Maria Goudesidou, Konstantina Kosma, Christalena Sofocleous, Periklis Makrythanasis

{"title":"Unraveling the Role of WDR91: Case Report of a Previously Unrecognized Clinical Entity.","authors":"Nikolaos M Marinakis, Afrodite Kampouraki, Danai Veltra, Faidon-Nikolaos Tilemis, Maria Vasilopoulou, Aikaterini Dokou, Elissavet Georgiadou, Euthalia Karavergou, Maria Christolouka, Alexis Alexopoulos, Dimitra Kirillidi, Maria Goudesidou, Konstantina Kosma, Christalena Sofocleous, Periklis Makrythanasis","doi":"10.1111/cge.70012","DOIUrl":"https://doi.org/10.1111/cge.70012","url":null,"abstract":"WDR91, a WD40 repeat domain-containing protein, is a key regulator of endosomal trafficking, lysosomal function, and autophagy. It acts as a Rab7 effector, forming a complex with WDR81 to modulate phosphatidylinositol 3-kinase (PI3K) activity, endosomal maturation, and lysosome homeostasis. Loss-of-function variants in WDR91 are considered related to endosomal accumulation, impaired cargo degradation, and neurodegeneration. In this report, an autosomal recessive neurodevelopmental disorder is proposed, associated with WDR91 loss-of-function in a consanguineous family. The patient presented with severe microcephaly, dysmorphic features, and organomegaly, along with early onset psychomotor delay, hypotonia, sensorineural hearing impairment, and visual impairment. Whole-exome sequencing (WES) identified a homozygous splice site variant, NM_014149.4:c.1395+1G>A, predicted to disrupt the donor site and classified as likely pathogenic (PVS1, PM2). The variant was absent from population databases and our internal in-house cohort. Functional analysis supports a pathogenic role for the variant. WDR91 deficiency results in neuronal loss, cortical thinning, and impaired brain development, as evidenced in Wdr91 knockout models. Our study expands the clinical and genetic spectrum of WDR91-related disorders and highlights the need for further investigations to elucidate the precise molecular mechanisms underlying WDR91-associated pathogenesis.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diagnostic Utility of Exome Data Reanalysis After In Silico Multi-Gene Panels or Clinical Exome Testing for Patients With Epilepsy and Developmental Delay/Intellectual Disability: A Retrospective Cohort Study. 多基因芯片或临床外显子组检测后外显子组数据再分析对癫痫和发育迟缓/智力残疾患者的诊断价值：一项回顾性队列研究

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-06-22 DOI: 10.1111/cge.70008

Alexanne Cuillerier, Andrea Goodman, Chloe Lawrence, Noémie Villeneuve-Cloutier, Christine M Armour, Priya T Bhola, Danielle K Bourque, Melissa T Carter, Joanna Lazier, Sarah L Sawyer, Maha Saleh, Chitra Prasad, Victoria M Siu, Kym M Boycott, Taila Hartley, David A Dyment, Tugce B Balci

{"title":"Diagnostic Utility of Exome Data Reanalysis After In Silico Multi-Gene Panels or Clinical Exome Testing for Patients With Epilepsy and Developmental Delay/Intellectual Disability: A Retrospective Cohort Study.","authors":"Alexanne Cuillerier, Andrea Goodman, Chloe Lawrence, Noémie Villeneuve-Cloutier, Christine M Armour, Priya T Bhola, Danielle K Bourque, Melissa T Carter, Joanna Lazier, Sarah L Sawyer, Maha Saleh, Chitra Prasad, Victoria M Siu, Kym M Boycott, Taila Hartley, David A Dyment, Tugce B Balci","doi":"10.1111/cge.70008","DOIUrl":"10.1111/cge.70008","url":null,"abstract":"Epilepsy is a relatively common condition with genetic factors contributing significantly to its etiology. Advances in next-generation sequencing have dramatically increased the number of known epilepsy genes, improving diagnostic capabilities and patient care. However, 50%-80% of epilepsy patients remain undiagnosed after genomic testing, which includes chromosomal microarray, multigene panels, and genome-wide sequencing. Reanalysis of existing exome sequencing data has shown promise in increasing diagnostic yield. In this study, we reanalyzed exome sequencing data from 87 individuals with unsolved epilepsy and developmental delay or intellectual disability in Ontario, Canada. Our approach combined clinical and translational research methodologies to identify genetic variants linked to epilepsy. We obtained a diagnostic yield of 14.9%, solving 13 participants, with 11 involving known genes and two novel gene discoveries. In addition, 11 potential diagnoses were identified, suggesting that further investigation could confirm additional diagnoses. Factors such as the inclusion of additional family data, new disease-gene associations, and technological advancements contributed to these findings. This study highlights the importance of reanalysis as a cost-effective and timely approach to improving diagnostic yield in epilepsy associated with neurodevelopmental delay.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-06-21 DOI: 10.1111/cge.70005

Adella Karam, Clarisse Delvallée, Bénédicte Gérard, Elodie Javey, Pascal Kessler, Valérie Pelletier, Jean-Baptiste Lamouche, Nicolas Le May, Jean Muller, Hélène Dollfus

{"title":"PIK3C2A-Related Clinical Phenotype and Cellular Charaterization Linked to Functional SHH Primary Cilia Defect.","authors":"Adella Karam, Clarisse Delvallée, Bénédicte Gérard, Elodie Javey, Pascal Kessler, Valérie Pelletier, Jean-Baptiste Lamouche, Nicolas Le May, Jean Muller, Hélène Dollfus","doi":"10.1111/cge.70005","DOIUrl":"10.1111/cge.70005","url":null,"abstract":"PIK3C2A is a member of the class II phosphatidylinositol-3-kinases (PI3K) family that catalyzes the phosphorylation of phosphatidylinositol (PI) into PI(3)P and of PI(4)P into PI(3,4)P2. These second messenger lipids regulate a wide range of downstream signaling pathways involved in many physiological functions and cellular processes, including cell proliferation, growth, survival, motility, and metabolism. PIK3C2A is also involved in the regulation of primary cilia formation and maintenance and in the regulation of receptor-mediated endocytosis at the base of the cilium. PIK3C2A was recently related to a novel oculoskeletodental syndrome (OCSKD MIM#618440), combining short stature, coarse facial features, ocular, and skeletal abnormalities. We describe here the fifth family presenting a PIK3C2A-related syndrome characterized by pulverulent cataracts and deafness. Using trio exome sequencing, we identified two novel compound heterozygous variants in PIK3C2A for which functional testing was necessary to assess the effect of one of the variants. Cellular studies of patient's-derived skin fibroblasts revealed a normal PIK3C2A protein level but a defective enzyme. Ciliary and cellular phenotype studies showed in the patient's cells impaired cilia formation and function as well as a reduced proliferative capacity. This study expands the clinical and mutational spectrum of PIK3C2A-related syndrome.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Highly Variable Expressivity of a CNV Deletion Involving TBX4 in Three Deceased Siblings With Lung Developmental Disorder and Their Mildly Affected Mother and Grandfather. 涉及TBX4的CNV缺失在三个患有肺发育障碍的已故兄弟姐妹及其轻度影响的母亲和祖父中的高度可变表达性

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-06-21 DOI: 10.1111/cge.70010

Przemyslaw Szafranski, Tomasz Gambin, Michal Kadlof, Michał Denkiewicz, Dariusz Plewczynski, Hyun Jeong Kim, Gail Deutsch, Nahir Cortes-Santiago, Salmo Raskin, Paweł Stankiewicz

{"title":"Highly Variable Expressivity of a CNV Deletion Involving TBX4 in Three Deceased Siblings With Lung Developmental Disorder and Their Mildly Affected Mother and Grandfather.","authors":"Przemyslaw Szafranski, Tomasz Gambin, Michal Kadlof, Michał Denkiewicz, Dariusz Plewczynski, Hyun Jeong Kim, Gail Deutsch, Nahir Cortes-Santiago, Salmo Raskin, Paweł Stankiewicz","doi":"10.1111/cge.70010","DOIUrl":"10.1111/cge.70010","url":null,"abstract":"Single nucleotide variants (SNVs) and copy-number variant (CNV) deletions involving TBX4 have been associated with pulmonary arterial hypertension, ischiocoxopodopatellar syndrome, and lethal lung developmental disorders (LLDDs). Thus far, all large CNV deletions encompassing entire TBX4 have been found to have arisen de novo. Here, we present a three-generation family with three neonate siblings who died within 35-66 days due to histopathologically diagnosed LLDD. Whole-genome sequencing identified an ~108-kb CNV deletion encompassing TBX4 in all three infants. The deletion was also found in their mother with a history of pneumonia and persistent thick upper airway secretions and in the maternal grandfather who had surgically corrected genu valgum. RT-qPCR from the proband's lung biopsy showed a decrease of TBX4 transcript level greater than 50%, suggesting additional deregulation of TBX4 expression. Computational analyses of the TBX4 super-enhancer identified 15 candidate noncoding hypomorphic SNVs transmitted to the children exclusively from their father and absent in their mother and maternal grandfather. We show that SNV rs35827636T > C, previously proposed as potentially hypomorphic in an unrelated AcDys patient, reduced transcriptional activity of the TBX4 promoter in an episomal reporter assay. Moreover, Hi-C analysis predicted inter-TAD interaction between the TBX4 super-enhancer and its promoter-proximal region. Our data further demonstrate complex compound inheritance of LLDDs and resulting challenges for genetic counseling.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical and Genetic Spectra of Progressive Familial Intrahepatic Cholestasis With Normal GGT: 31 Pediatric Patients and 16 Novel Variants. 伴有正常GGT的进行性家族性肝内胆汁淤积症的临床和遗传谱：31例儿科患者和16例新变体

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-06-19 DOI: 10.1111/cge.70004

Nehal M Elkoofy, Mortada H El-Shabrawi, Mohamed A Elmonem

{"title":"Clinical and Genetic Spectra of Progressive Familial Intrahepatic Cholestasis With Normal GGT: 31 Pediatric Patients and 16 Novel Variants.","authors":"Nehal M Elkoofy, Mortada H El-Shabrawi, Mohamed A Elmonem","doi":"10.1111/cge.70004","DOIUrl":"10.1111/cge.70004","url":null,"abstract":"Progressive familial intrahepatic cholestasis (PFIC) syndromes are rare autosomal recessive disorders. We present the first detailed phenotype-genotype of PFIC children with normal gamma-glutamyltransferase (GGT) [normal GGT/PFIC] in an African population. Thirty-one pediatric patients belonging to 28 unrelated Egyptian families with normal GGT/PFIC were reported. Clinical, biochemical, histopathological, and genetic data were systematically analyzed. Patients were 15 males/16 females (55 ± 52 months at diagnosis). Apart from cholestasis, clinical features included severe pruritus (visual analogue scale 7.5 ± 3.4), hepatomegaly (80.6%), sleep deprivation (41.9%), and splenomegaly (19.4%). 13/28 families had ABCB11 variants (PFIC2), 6/28 families had ATP8B1 (PFIC1) and TJP2 (PFIC4) variants each, 2/28 had MYO5B variants (PFIC10), and one family had USP53 variants (PFIC7). Twenty-five disease-causing variants were reported, including 16 novel variants. PFIC1 patients were more severely affected compared to other PFIC syndromes, as the incidence of growth retardation, sibling deaths, skin changes, and progression to biliary diversion were all significantly higher (p value 0.006, 0.012, 0.037, and 0.012, respectively). In contrast, none of the 13 PFIC2 children progressed to biliary diversion, and all four PFIC10 children had normal liver transaminases. Our study expands the global phenotypic and genotypic knowledge of normal GGT/PFIC and will facilitate better care for the syndrome in Egypt.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Atypical Presentation of Homozygous UROD Mutation: Porphyria Cutanea Tarda or Mild Hepatoerythropoietic Porphyria? 纯合子UROD突变的不典型表现：迟发性皮肤卟啉症还是轻度肝促红细胞生成性卟啉症？

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-06-19 DOI: 10.1111/cge.70007

Pedro Gabriel Dotto, Mônica Ribeiro de Azevedo Vasconccellos, José Francisco da Silva Franco, Caio Perez Gomes, João Bosco Pesquero

引用次数: 0