Molecular Genetics & Genomic Medicine最新文献

{"title":"Deciphering Growth Patterns in Korean Children With Sotos Syndrome Through the Development of a Disease-Specific Growth Chart.","authors":"Naye Choi, Hwa Young Kim, Jung Min Ko","doi":"10.1002/mgg3.70028","DOIUrl":"10.1002/mgg3.70028","url":null,"abstract":"<p><strong>Background: </strong>Sotos syndrome (SS) is a rare disorder characterized by overgrowth, distinctive facial features, and intellectual disability that is primarily caused by NSD1 pathogenic variants or 5q35 microdeletions.</p><p><strong>Methods: </strong>We retrospectively analyzed the clinical characteristics and 339 anthropometric measurements over an average of 4.3 years of follow-up in 57 Korean children with SS. Sex-specific percentile curves for height, weight, and head circumference were developed using a generalized additive model that included factors such as location, scale, and shape.</p><p><strong>Results: </strong>Males with SS demonstrated higher height before the age of 12.0, greater weight before 10.0, and larger head circumference before 15.5 compared to age- and sex-matched controls. Females with SS displayed higher height before 17.0, greater weight before 10.5, and larger head circumference before 12.0 compared to controls. Bone age was advanced compared to chronological age in 40% of males and 8% of females at their last visit. The predicted and target adult heights were not significantly different between groups. In subgroup analysis, the intragenic variant group (n = 48) showed a higher mean standard deviation score of height and weight in males, and head circumference in females compared to the microdeletion group (n = 9).</p><p><strong>Conclusions: </strong>Korean children with genetically confirmed SS exhibited overgrowth in height, weight, and head circumference. Overgrowth phenotypes were more prominent in patients with NSD1 intragenic variants than in those with microdeletions. This is the first study to provide reference data on the growth of Korean children with SS.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Pathology of Myotonic Dystrophy Type 1 in Iceland.","authors":"E G Hallgrímsdóttir, H Svansson, V F Stefánsdóttir, Ó Á Sveinsson, H Ólafsdóttir, E Briem, S Sveinbjörnsdóttir, J J Jónsson","doi":"10.1002/mgg3.70013","DOIUrl":"10.1002/mgg3.70013","url":null,"abstract":"<p><strong>Background: </strong>Myotonic Dystrophy type 1 (DM1) is an autosomal dominant disease with anticipation due to increased number of CTG repeats in the DMPK gene.</p><p><strong>Methods: </strong>This retrospective, cohort study in Iceland assessed prevalence of DM1, molecular pathology, and patient ascertainment. Data was collected from all major hospitals in Iceland, Medical Director of Health, and independent clinics. Cohort criteria were diagnosis of DM1 on January 1, 2021, or time of death. Population-based Icelandic Genealogy Database of the Genetical Committee at the University of Iceland was used for genealogy.</p><p><strong>Results: </strong>In Iceland, 221 individuals, including 19 obligate carriers, had been diagnosed with DM1 of which 144 were alive giving a point prevalence of 39 per 100,000 (four times the world average of 9.3). Genealogy analysis identified 45 first-degree families. Age-adjusted prevalence ranged between 11 and 66 per 100,000. Average potential years of life lost were 20.5 per person. Where information was available, 63% of ascertainment was based on family history in cascade testing.</p><p><strong>Conclusion: </strong>The differences in age-adjusted prevalence suggest that the overall point prevalence is an underestimation due to underdiagnosis in younger age groups and lethality in oldest age group. Our data supports use of cascade testing to improve DM1 ascertainment.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Correlation, Shared Loci, and Causal Relationship Between Bullous Pemphigoid and Atopic Dermatitis: A Large-Scale Genome-Wide Cross-Trait Analysis.","authors":"Qing Wang, Xuehua Wang, Qizhen Zhuang, Yuan Wu, Junhong Zhang, Yue Lu, Jingjing Wu, Juanjuan Liu, Xiangyu Hu, Ling Han","doi":"10.1002/mgg3.70022","DOIUrl":"https://doi.org/10.1002/mgg3.70022","url":null,"abstract":"<p><strong>Background: </strong>Bullous pemphigoid (BP) and atopic dermatitis (AD) are currently thought to be tightly related, yet studies of the mechanisms of co-morbidities are lacking.</p><p><strong>Methods: </strong>We obtained GWAS data for BP (N = 376,274) and AD (N = 796,661) from the Finnish Genetic Research Program dataset and the UK Biobank, separately. Then, the following four analyses were performed: (1) cross-trait linkage disequilibrium score regression (LDSC) to assess the genetic correlation between BP and AD, (2) cross-phenotype association analysis (CPASSOC) to identify multiple effector loci shared by BP and AD, (3) transcriptome-wide association study (TWAS) to determine whether their cross-organizational expression patterns share genes with a common biological mechanism of relevance, and (4) bidirectional Mendelian randomization (MR) analysis to assess bidirectional causal effects of BP and AD.</p><p><strong>Results: </strong>We found a positive genetic association between BP and AD (rg = 0.5476, p = 0.0495) as well as identified four pleiotropic loci and 59 common genes affecting BP and AD. Bidirectional MR analysis suggested that BP promotes the risk of AD.</p><p><strong>Conclusions: </strong>We revealed a genetic link between BP and AD, which is associated with biological pleiotropy and causality. Awareness of the association between BP and AD helps dermatologists manage patients with these illnesses.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep Sequencing and Phenotyping in an Australian Tuberous Sclerosis Complex \"No Mutations Identified\" Cohort.","authors":"Clara W T Chung, Adam M Bournazos, Lok Chi Denise Chan, Vanessa Sarkozy, John Lawson, Sean E Kennedy, Sandra T Cooper, Edwin P Kirk, David Mowat","doi":"10.1002/mgg3.70017","DOIUrl":"10.1002/mgg3.70017","url":null,"abstract":"<p><p>Tuberous sclerosis complex (TSC) is a variable multisystem disorder. The \"no mutations identified\" (NMI) group are reportedly phenotypically milder than those with an identified molecular cause, and often have mosaic or intronic variants not detected by standard sequencing methods.</p><p><strong>Methods: </strong>We describe the phenotypes in an Australian TSC NMI group (n = 18) and a molecular testing strategy implementable in a diagnostic laboratory. Massively parallel sequencing (MPS) of the whole genomic regions of TSC1 and TSC2 was performed using DNA extracted from multiple tissue samples per participant.</p><p><strong>Results: </strong>Our study showed that the phenotype in TSC NMI individuals can be similar to those with heterozygous, particularly TSC1, variants. Although neurodevelopmental outcomes can be less severe, the number of organ systems involved was similar to the non-mosaic groups. A diagnostic yield of 72% (13/18) was achieved, with the majority (10/13) being mosaic variants and the remainder heterozygous variants missed on previous testing.</p><p><strong>Conclusion: </strong>Testing DNA from multiple tissue samples allowed for validation of otherwise discarded low-level mosaic variants and detection of mosaic variants by MPS without excessive cost or the need for specialised techniques. Implementing this approach in a diagnostic setting is viable and allows optimal clinical care of patients with NMI TSC.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atypical Presentation of Congenital Insensitivity to Pain With Anhidrosis Leading to Diagnostic Odyssey.","authors":"Tomoyasu Higashimoto, Martin E Garber, Lauren Hipp, Jenna Damon, Qing Li","doi":"10.1002/mgg3.70027","DOIUrl":"10.1002/mgg3.70027","url":null,"abstract":"<p><strong>Background: </strong>Congenital insensitivity to pain with anhidrosis (CIPA) (OMIM 256800) is a rare autosomal-recessive condition, also known as hereditary sensory and autonomic neuropathy type IV (HSAN-IV). The most commonly reported features include anhidrosis, intellectual disability, self-mutilation, febrile episodes, impaired temperature perception, recurrent infections and/or autonomic nervous system impairment. Major joint destruction and joint deformity known as Charcot (neuropathic) joints are also seen in CIPA patients attributed to insensitivity to joint pain.</p><p><strong>Methods: </strong>We present a case of a 46-year-old female affected with CIPA with a known NTRK1 variant and previously unidentified variant. Minigene reporter constructs were generated encompassing the exon 8 to exon 13 of the NTRK1 gene using the reference sequence and one harboring c.1483 + 5G > A variant identified in our proband. Minigene constructs were transfected into HEK293T cells, and the transcript was analysed for splicing to evaluate the effect of this variant in splicing.</p><p><strong>Results: </strong>The patient (46-year-old female) exhibited right ankle joint deformity around 5 years of age. Patient also experienced lumbar compression and knee damage in adulthood. She had undergone a significant number of evaluations without clear diagnosis. Her presentation lacked many of the common clinical presentations of CIPA, and therefore, the focus of her evaluation was directed towards her unexplained joint deformities. Exome sequencing revealed a known pathogenic variant in NTRK1 (c.851 - 33T > A:p.? [Intron 7]) and a novel NTRK1 variant (c.1483 + 5G > A:p.? [Intron 11]), which was later re-classified as likely pathogenic. The patient was started on a biologic disease-modifying anti-rheumatic medication (bDMARD) due to a possible inflammatory etiology of her joint deformity. Molecular diagnosis allowed for modification of her treatment and surveillance strategies. Our minigene splicing assay demonstrated that the presence of the c.1483 + 5G > A variant has a negative effect on splicing, supporting the pathogenicity of this novel variant.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Pathogenic Copy Number Variants in Mexican Patients With Inherited Retinal Dystrophies Applying an Exome Sequencing Data-Based Read-Depth Approach.","authors":"Gerardo E Fabian-Morales, Vianey Ordoñez-Labastida, Froylan Garcia-Martínez, Luis Montes-Almanza, Juan C Zenteno","doi":"10.1002/mgg3.70019","DOIUrl":"https://doi.org/10.1002/mgg3.70019","url":null,"abstract":"<p><strong>Background: </strong>Retinal dystrophies (RDs) are the most common cause of inherited blindness worldwide and are caused by genetic defects in about 300 different genes. While targeted next-generation sequencing (NGS) has been demonstrated to be a reliable and efficient method to identify RD disease-causing variants, it doesn't routinely identify pathogenic structural variant as copy number variations (CNVs). Targeted NGS-based CNV detection has become a crucial step for RDs molecular diagnosis, particularly in cases without identified causative single nucleotide or Indels variants. Herein, we report the exome sequencing (ES) data-based read-depth bioinformatic analysis in a group of 30 unrelated Mexican RD patients with a negative or inconclusive genetic result after ES.</p><p><strong>Methods: </strong>CNV detection was performed using ExomeDepth software, an R package designed to detect CNVs using exome data. Bioinformatic validation of identified CNVs was conducted through a commercially available CNV caller. All identified candidate pathogenic CNVs were orthogonally verified through quantitative PCR assays.</p><p><strong>Results: </strong>Pathogenic or likely pathogenic CNVs were identified in 6 out of 30 cases (20%), and of them, a definitive molecular diagnosis was reached in 5 cases, for a final diagnostic rate of ~17%. CNV-carrying genes included CLN3 (2 cases), ABCA4 (novel deletion), EYS, and RPGRIP1.</p><p><strong>Conclusions: </strong>Our results indicate that bioinformatic analysis of ES data is a reliable method for pathogenic CNV detection and that it should be incorporated in cases with a negative or inconclusive molecular result after ES.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acromesomelic Dysplasia With Homozygosity for a Likely Pathogenic BMPR1B Variant: Postaxial Polydactyly as a Novel Clinical Finding.","authors":"Ibrahim M Abdelrazek, Alexej Knaus, Behnam Javanmardi, Peter M Krawitz, Denise Horn, Ebtesam M Abdalla, Sheetal Kumar","doi":"10.1002/mgg3.70023","DOIUrl":"https://doi.org/10.1002/mgg3.70023","url":null,"abstract":"<p><strong>Background: </strong>Acromesomelic chondrodysplasias are a rare subgroup of the clinically and genetically heterogeneous osteochondrodysplasias that are characterised by abnormalities in the limb development and short stature. Here, we report a 2-year-old boy, offspring of consanguineous parents, with acromesomelic dysplasia and postaxial polydactyly in which exome sequencing identified a novel homozygous missense variant in BMPR1B. The patient showed skeletal malformation of both hands and feet that included complex brachydactyly with the thumbs most severely affected, postaxial polydactyly of both hands, shortened toes as well as a bilateral hypoplasia of the fibula.</p><p><strong>Methods: </strong>Whole trio exome sequencing was conducted to identify potential genetic variants in the patient.</p><p><strong>Results: </strong>The analysis identified the biallelic variant NM_001203.3:c.821A > G;p.(Gln274Arg) in BMPR1B, a gene encoding bone morphogenetic protein receptor 1B.</p><p><strong>Conclusion: </strong>The skeletal phenotype can be brought in line with the phenotypes of previously reported cases of BMPR1B-associated chondrodysplasias. However, the postaxial polydactyly described here is a novel clinical finding in a BMPR1B-related case; notably, it has previously been reported in other acromesomelic dysplasia cases caused by homozygous pathogenic variants in GDF5-a gene which encodes for growth differentiation factor 5, a high-affinity ligand to BMPR1B.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tremor Ataxia With Central Hypomyelation Phenotype Related to a Recurrent POLR3A Mutation in Six Unrelated Tunisian Families.","authors":"Ichraf Kraoua, Maha Jamoussi, Cyrine Drissi, Lilia Kraoua, Séverine Drunat, Hanene Benrhouma, Thouraya Ben Younes, Sonia Nagi, Sonia Abdelhak, Odile Boespflug Tanguy, Ilhem Ben Youssef-Turki, Mediha Trabelsi, Imen Dorboz","doi":"10.1002/mgg3.70007","DOIUrl":"10.1002/mgg3.70007","url":null,"abstract":"<p><strong>Background: </strong>POLIII-related leukodystrophies are a group of recently recognized hereditary white matter diseases with a similar clinical and radiological phenotype. No Tunisian studies have been published about POLIII-related leukodystrophy due to POLR3A variants. The aim of this study was to contribute to the clinical, radiological, and genetic characterization of POLR3A-related leukodystrophy in a Tunisian cohort.</p><p><strong>Methods: </strong>We report six cases of genetically confirmed POLR3A-related leukodystrophy belonging to six unrelated Tunisian families, along with a review of previously published pediatric cases.</p><p><strong>Results: </strong>All patients were born to consanguineous marriages and originated from the North or the Center of Tunisia. Age at onset varied between 15 months and 6 years. The clinical phenotype was similar in all patients with cerebellar ataxia, tremor, and nystagmus being the key features. Brain imaging showed diffuse hypomyelination in all patients with progressive cerebellar atrophy in three patients. Molecular analysis identified the same bi-allelic NM_007055.4:c.2011T>C; p.(Trp671Arg) variant in the POLR3A gene in all patients.</p><p><strong>Conclusion: </strong>We hypothesize a founder effect for the identified variant given its recurrence in six unrelated individuals with a similar clinical phenotype. Given the apparent genetic homogeneity of Tunisian POLR3A patients, the recurrent variant should be directly targeted. This should facilitate diagnosis in index patients, and genetic counseling.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Systematic Review Exploring Empirical Pharmacogenomics Research Within Global Indigenous Populations.","authors":"Bushra Farah Nasir, Ritwika Vinayagam, Luciana Massi, Shivashankar H Nagaraj, Maree Toombs, Kym M Rae","doi":"10.1002/mgg3.70018","DOIUrl":"10.1002/mgg3.70018","url":null,"abstract":"<p><strong>Background: </strong>This systematic review aims to highlight the scope of pharmacogenomics research within global Indigenous populations. This review also explores the barriers and facilitators of pharmacogenomics research within this population.</p><p><strong>Methodology: </strong>A systematic review of literature was conducted to identify and present an understanding of current empirical evidence demonstrating the conduct of genomics or pharmacogenomics research within global Indigenous populations (PROSPERO registration: CRD42021257226). Using key search terms, relevant databases were searched for articles published between January 2010 and July 2022. Screening, data extraction, and analysis was conducted using well-defined inclusion criteria. Quality assessment and risk of bias appraisal was conducted using the mixed methods appraisal tool. Indigenous community engagement and participation in genomics research was assessed using the social-ecological framework.</p><p><strong>Results: </strong>From the 427 articles identified, 77 articles met inclusion criteria and underwent full-text screening. Of these, 30 articles were included in the final review, with 16 being quantitative and 14 either qualitative or mixed methods studies. Most studies were conducted with native Indigenous populations from the United States of America (36%). Content analysis revealed that studies either explored genetic variations associated with disease in Indigenous populations (23%) or markers for drug metabolism (30%) or were designed to understand perspectives of genomics research within this population (47%). Perspectives included the exploration of the role of participants in research, benefits or outcomes achieved from participation in genomics research, and levels of Indigenous engagement and participation in genomics research.</p><p><strong>Conclusions: </strong>This review highlights a growing gap in Indigenous genomics research globally. It presents several important considerations from Indigenous participants, identifying how researchers can co-create culturally safe and inclusive design, implementation, analysis, and subsequent outcomes of genomics research involving Indigenous people. Indigenous governance, self-determination and leadership is essential, with researchers required to be responsive to such fundamental partnerships for research to progress.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extremely Low Birth Weight Infant (Gestational Age of 29 Weeks) With Kabuki Syndrome Type I: Case Report and Literature Review.","authors":"Qi Li, Yuzhu Zheng, Xinyuan Guo, Jiang Xue","doi":"10.1002/mgg3.70025","DOIUrl":"10.1002/mgg3.70025","url":null,"abstract":"<p><strong>Background: </strong>This paper aimed to investigate the clinical phenotype of Kabuki syndrome (KS) in premature infants.</p><p><strong>Methods: </strong>This paper presents a case of an extremely low birth weight infant (gestational age 29 weeks) with KS1 caused by a variant in the KMT2D gene. The clinical, pathological, and differential diagnostic findings were comprehensively analyzed. A thorough literature review was also performed to enhance the understanding of KS, revealing its unique features and prognostic significance.</p><p><strong>Results: </strong>The infant was a male with a gestational age of 29 weeks and a birth weight of 850 g. He had intrauterine growth retardation, characterized by cleft palate, sacrococcygeal skin depressions, and recurrent metabolic acidosis. Whole-exome sequencing revealed the c.4267C > T (p.Arg1423Cys) variant in the KMT2D gene, which was absent in his parents. The patient was discharged after 67 days of treatment, and he was followed up to 19 months of corrected gestational age, with growth retardation and expression language delay. Ten previous studies on preterm infants were retrieved, with 10 preterm infants. They all had characteristic facial features, such as long blepharophimosis, sparse and lateral 1/3 eyebrows, and large and prominent/cupped ears. Other manifestations were extrauterine growth delay (7/10), abnormal development of the cardiovascular system (7/10), abnormal development of the nervous system (5/10), and cleft palate (2/10).</p><p><strong>Conclusions: </strong>Kabuki syndrome is a rare hereditary disorder involving multiple organs and systems. Genetic assessment for preterm infants with congenital abnormalities is recommended.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}