475 results match your criteria Holt-Oram Syndrome


variant with the novel phenotype of mixed‑type total anomalous pulmonary venous return in Holt‑Oram Syndrome and variable intrafamilial heart defects.

Mol Med Rep 2022 Jun 6;25(6). Epub 2022 May 6.

Pediatric Genomics Discovery Program, Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06504, USA.

Variants in T‑box transcription factor 5 () can result in a wide phenotypic spectrum, specifically in the heart and the limbs. has been implicated in causing non‑syndromic cardiac defects and Holt‑Oram syndrome (HOS). The present study investigated the underlying molecular etiology of a family with heterogeneous heart defects. Read More

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Congenital Disorders of the Pediatric Thumb.

JBJS Rev 2022 03 1;10(3). Epub 2022 Mar 1.

Scottish Rite for Children, Dallas, Texas.

»: Surgical timing for pediatric trigger thumb treatment is controversial for numerous reasons including the potential for spontaneous resolution, the possibility of bilateral involvement, and anesthesia concerns regarding the developing brain. Hence, a reasonable approach is to delay the surgical procedure until the patient is ≥3 years of age.

»: Preaxial polydactyly is usually unilateral and sporadic, with the most common reconstruction method consisting of excision of the diminutive thumb with preservation and soft-tissue reconstruction of the dominant thumb. Read More

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Generation of a CRISPR/Cas edited human induced pluripotent stem cell line DHMi005-A-1 carrying a patient-specific disease-causing point mutation in the TBX5 gene.

Stem Cell Res 2022 04 27;60:102691. Epub 2022 Jan 27.

Technical University of Munich, School of Medicine & Health, Department of Cardiovascular Surgery, Institute Insure, German Heart Center Munich, Lazarettstrasse 36, 80636 Munich, Germany.

A number of mutations in the human TBX5 gene have been described which cause Holt-Oram syndrome, a severe congenital disease associated with abnormalities in heart and upper limb development. We have used a prime-editing approach to introduce a patient-specific disease-causing TBX5 mutation (c.920_C > A) into an induced pluripotent stem cell (iPSC) line from a healthy donor. Read More

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Patient-Specific TBX5-G125R Variant Induces Profound Transcriptional Deregulation and Atrial Dysfunction.

Circulation 2022 02 3;145(8):606-619. Epub 2022 Feb 3.

Department of Medical Biology (A.F.vO., F.M.B., K.vD., K.T.S., V.W., J-S.U., A.V.P., P.B., A.O.V., B.J.B., V.M.C.), University of Amsterdam, The Netherlands.

Background: The pathogenic missense variant p.G125R in TBX5 (T-box transcription factor 5) causes Holt-Oram syndrome (also known as hand-heart syndrome) and early onset of atrial fibrillation. Revealing how an altered key developmental transcription factor modulates cardiac physiology in vivo will provide unique insights into the mechanisms underlying atrial fibrillation in these patients. Read More

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February 2022

A genotype-first analysis in a cohort of Mullerian anomaly.

J Hum Genet 2022 Jan 13. Epub 2022 Jan 13.

Department of Obstetrics and Gynaecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.

Müllerian anomaly (M.A.) is a group of congenital anatomic abnormalities caused by aberrations of the development process of the Müllerian duct. Read More

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January 2022

Identification of deleterious single nucleotide polymorphism (SNP)s in the human gene & prediction of their structural & functional consequences: An approach.

Biochem Biophys Rep 2021 Dec 2;28:101179. Epub 2021 Dec 2.

Department of Biotechnology and Genetic Engineering, Faculty of Life Science, University of Development Alternative, Dhaka, 1209, Bangladesh.

T-box transcription factor 5 gene () encodes the transcription factor TBX5, which plays a crucial role in the development of heart and upper limbs. Damaging single nucleotide variants in this gene alter the protein structure, disturb the functions of TBX5, and ultimately cause Holt-Oram Syndrome (HOS). By analyzing the available single nucleotide polymorphism information in the dbSNP database, this study was designed to identify the most deleterious SNPs through approaches and predict their structural and functional consequences. Read More

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December 2021

Atrial myopathy: A primary substrate for atrial fibrillation.

Heart Rhythm 2022 03 11;19(3):476-477. Epub 2021 Dec 11.

Inherited Arrhythmia and Cardiomyopathy Program, Arrhythmia Service, Division of Cardiology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada. Electronic address:

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Establishment of a patient-specific induced pluripotent stem cell line DHMi004-A from a male Holt-Oram syndrome patient with verified TBX5 mutation.

Stem Cell Res 2022 01 6;58:102617. Epub 2021 Dec 6.

DZHK (German Center for Cardiovascular Research) - Partner Site Munich Heart Alliance, Munich, Germany; Division of Cardiac Surgery, Yale University School of Medicine, New Haven, CT, USA.

The Holt-Oram syndrome (HOS) is a rare autosomal dominant disorder, mostly based on mutations in the TBX5 gene. Patients show malformation of at least one upper limb along with congenital heart defects. The established induced pluripotent stem cell (iPSC) line was generated from a patient displaying pronounced and typical features of HOS and carrying a single-nucleotide change c. Read More

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January 2022

Familial atrial myopathy in a large multigenerational heart-hand syndrome pedigree carrying an LMNA missense variant in rod 2B domain (p.R335W).

Heart Rhythm 2022 03 20;19(3):466-475. Epub 2021 Nov 20.

Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China. Electronic address:

Background: The literature on laminopathy with ventricular phenotype is extensive. However, the pathogenicity of LMNA variations in atrial lesions still lacks research.

Objective: The purpose of this study was to characterize the atrial phenotypes and possible mechanisms in a large Chinese family with heart-hand syndrome carrying a LMNA missense variant in rod 2B domain (c. Read More

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Prenatal Diagnosis of Holt-Oram Syndrome With a Novel Mutation of Gene: A Case Report.

Front Pediatr 2021 19;9:737633. Epub 2021 Oct 19.

Department of Ultrasound, Women and Children's Hospital of Sichuan, Chengdu, China.

Holt-Oram syndrome (HOS) is an autosomal dominant disorder caused by mutations of gene. We report a fetus with HOS diagnosed sonographically at 23 weeks of gestation. The fetal parents are non-consanguineous. Read More

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October 2021

Holt-Oram syndrome, bicuspid aortic valve, and patent ductus arteriosus.

Kardiol Pol 2021;79(12):1395-1396. Epub 2021 Oct 2.

Department of Interventional Cardiology and Angiology, National Institute of Cardiology, Warszawa, Poland.

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Identification of a novel TBX5 c.755 + 1 G > A variant and related pathogenesis in a family with Holt-Oram syndrome.

Am J Med Genet A 2022 01 6;188(1):58-70. Epub 2021 Sep 6.

Research Center for Reproductive Medicine, Shantou University Medical College, Shantou, China.

The proband with congenital heart disease and abnormal thumb was clinically diagnosed as Holt-Oram syndrome (HOS). A novel variant, T-box transcription factor 5 (TBX5) c.755 + 1 G > A, was identified in the proband via whole exome sequencing and validated using Sanger sequencing. Read More

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January 2022

Diagnosis of absent right superior vena cava with intraoperative transesophageal echocardiography in a child with Holt-Oram syndrome: Anesthetic and perfusion implications.

Ann Card Anaesth 2021 Jul-Sep;24(3):358-361

Department of Anesthesiology and Critical Care, All India Institute of Medical Sciences (AIIMS) Bhubaneswar, Bhubaneswar, Odisha, India.

Holt-Oram syndrome is a rare autosomal disorder with cardiac, vascular, and upper limb anomalies. Previous reports have described anesthetic and perioperative challenges including difficulty in arterial and venous cannulations, airway management and rhythm, and temperature abnormalities. There are no previous reports of absent right superior vena cava (SVC) in children with Holt-Oram syndrome. Read More

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November 2021

Congenital extremity anomalies with a TBX5 pathogenic variant in consecutive IVF assisted pregnancies: a case report of Holt-Oram Syndrome.

J Obstet Gynaecol 2022 Apr 23;42(3):524-526. Epub 2021 Jun 23.

Department of OB/GYN, Yale New Haven Health, Bridgeport Hospital, Bridgeport, CT, USA.

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Combined clinic and home-based therapeutic approach for the treatment of bilateral radial deficiency for a young child with Holt-Oram syndrome: A case report.

J Hand Ther 2021 Mar 6. Epub 2021 Mar 6.

NYU Langone Health Rusk Rehabilitation, New York, NY, USA. Electronic address:

Background: Holt-Oram syndrome (HOS) is a rare, genetic condition characterized by the combination of congenital heart defect and hypoplasia in one or both upper extremities. Children with HOS commonly present with varied joint and limb involvement including radial longitudinal deficiency impacting hand function. Evidence-based guidelines regarding orthotic wear and therapeutic techniques are lacking. Read More

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TBX3 and TBX5 duplication: A family with an atypical overlapping Holt-Oram/ulnar-mammary syndrome phenotype.

Eur J Med Genet 2021 Jul 27;64(7):104213. Epub 2021 Apr 27.

Department of Clinical Genetics, Guy's Hospital, London, UK. Electronic address:

Holt-Oram syndrome (HOS) is a rare, autosomal dominant heart-hand syndrome caused by mutations in the TBX5 gene. A wide spectrum of TBX5 mutations have been reported previously, most resulting in a null allele leading to haploinsufficiency. TBX5 gene duplications have been previously reported in association with typical and atypical HOS phenotypes. Read More

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Functional analysis of two novel TBX5 variants present in individuals with Holt-Oram syndrome with different clinical manifestations.

Mol Genet Genomics 2021 Jul 17;296(4):809-821. Epub 2021 Apr 17.

Centre of Marine Sciences (CCMAR), University of Algarve, Faro, Portugal.

Holt-Oram syndrome (HOS) is a rare disorder characterized by cardiac and upper-limb defects. Pathogenic variants in TBX5-a gene encoding a transcription factor important for heart and skeletal development-are the only known cause of HOS. Here, we present the identification and functional analysis of two novel TBX5 pathogenic variants found in two individuals with HOS presenting distinct phenotypes. Read More

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Generation of a TBX5 homozygous knockout embryonic stem cell line (WAe009-A-45) by CRISPR/Cas9 genome editing.

Stem Cell Res 2021 03 6;51:102156. Epub 2021 Jan 6.

Anzhen Hospital, Capital Medical University, Beijing 100029, China. Electronic address:

Holt-Oram syndrome (HOS), which is caused by genetic changes in the TBX5 gene, affects the hands and heart. HOS patients have heart defects, including atrial septal defects (ASD), ventricular septal defects (VSD) and heart conduction disease. Here, we generated a homozygous TBX5 knockout human embryonic stem cell (hESC) line (TBX5-KO) using a CRISPR/Cas9 system. Read More

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Micromelic upper limbs and cardiac defect: A fetal case of Holt-Oram syndrome identified in the first trimester.

Eur J Obstet Gynecol Reprod Biol 2021 Mar 19;258:471-473. Epub 2021 Jan 19.

Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou, China. Electronic address:

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A novel TBX5 mutation predisposes to familial cardiac septal defects and atrial fibrillation as well as bicuspid aortic valve.

Genet Mol Biol 2020 13;43(4):e20200142. Epub 2020 Nov 13.

Fudan University, Department of Cardiology, Shanghai Fifth People's Hospital, Shanghai, China.

TBX5 has been linked to Holt-Oram syndrome, with congenital heart defect (CHD) and atrial fibrillation (AF) being two major cardiac phenotypes. However, the prevalence of a TBX5 variation in patients with CHD and AF remains obscure. In this research, by sequencing analysis of TBX5 in 178 index patients with both CHD and AF, a novel heterozygous variation, NM_000192. Read More

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November 2020

Heart-hand Syndrome.

Intern Med 2021 May 7;60(10):1651-1652. Epub 2020 Dec 7.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Japan.

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Clinical and epidemiological features of heart-hand syndrome, an updated analysis in China.

BMC Musculoskelet Disord 2020 Nov 25;21(1):777. Epub 2020 Nov 25.

Department of Hand Surgery, Beijing Ji Shui Tan Hospital, Xin jie kou dong jie 31, Xi Cheng Qu, Beijing, 100035, China.

Background: The purpose of this study was to prospectively recruit patients treated with limb malformation and to explore the prevalence and the clinical and epidemiological features of Heart-Hand Syndrome (HHS) in China.

Methods: The consecutive patients treated for congenital upper limb malformation in Beijing Ji Shui Tan Hospital from October 1st, 2016 to October 1st, 2019 were prospectively recruited. We reviewed the patients' medical records and identified patients with abnormal electrocardiogram (ECG) and/or abnormal ultrasonic cardiogram as well as their basic demographic and clinical characteristics. Read More

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November 2020

Transcriptional regulation of human T-box 5 gene (TBX5) by bone- and cardiac-related transcription factors.

Gene 2021 Feb 19;768:145322. Epub 2020 Nov 19.

Centre of Marine Sciences (CCMAR), University of Algarve, Faro, Portugal; Faculty of Medicine and Biomedical Sciences, University of Algarve, Faro, Portugal; Algarve Biomedical Centre (ABC) University of Algarve, Faro, Portugal; Centre for Biomedical Research (CBMR), University of Algarve, Faro, Portugal. Electronic address:

T-box 5 (TBX5) protein belongs to the T-box family whose members play a crucial role in cell-type specification, morphogenesis and organogenesis. TBX5 is a transcription factor important for cardiac development and upper limbs formation and its haploinsufficiency causes Holt-Oram syndrome (HOS). An increase in TBX5 dosage also leads to HOS, suggesting that TBX5 is a dose-sensitive transcription factor that needs to be tightly regulated but the molecular mechanisms involved remain unclear. Read More

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February 2021

Association of Radial Longitudinal Deficiency and Thumb Hypoplasia: An Update Using the CoULD Registry.

J Bone Joint Surg Am 2020 Oct;102(20):1815-1822

Children's Hospital Boston, Boston, Massachusetts.

Background: Deficiency of the radial aspect of the forearm and hand is the most common congenital longitudinal deficiency of the upper limb. Radial longitudinal deficiency is associated with several named syndromes. The purpose of the present study was to explore patterns of radial longitudinal deficiency and thumb hypoplasia in syndromes and to examine the severity of these differences across various syndromes. Read More

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October 2020

Steroid-associated bradycardia in a newly diagnosed B precursor acute lymphoblastic leukemia patient with Holt-Oram syndrome.

Ann Pediatr Cardiol 2020 Jul-Sep;13(3):241-243. Epub 2020 Jun 2.

Department of Pediatrics, Rush University Medical Center, Chicago, IL, USA.

Holt-Oram syndrome (HOS) (OMIM#142900) is a rare condition with upper extremity malformations as well as structural and conduction cardiac anomalies. There are sparse reports in the literature documenting malignancy in association with HOS. We report a pediatric patient clinically diagnosed with HOS (missing thumbs bilaterally, atrial septal defect, ventricular septal defect, and first-degree heart block), who also developed B precursor acute lymphoblastic leukemia. Read More

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Congenital superior oblique palsy in a patient with Holt-Oram syndrome.

Neurol Sci 2021 01 24;42(1):373-375. Epub 2020 Jul 24.

Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.

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January 2021

Familial dilated cardiomyopathy associated with pathogenic TBX5 variants: Expanding the cardiac phenotype associated with Holt-Oram syndrome.

Am J Med Genet A 2020 07 25;182(7):1725-1734. Epub 2020 May 25.

West of Scotland Clinical Genetics Service, Queen Elizabeth University Hospital, Glasgow, UK.

Holt-Oram syndrome (HOS) is a rare, autosomal dominant disorder caused by heterozygous pathogenic variants in cardiac T-box transcription factor, TBX5. Classically, it is associated with upper limb malformations and variable cardiac abnormalities. Limb manifestations are considered to be invariably present, ranging in severity from limitation in movement, to triphalangeal thumbs, absent thumbs, shortened forearms, or phocomelia. Read More

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Individual Limb Muscle Bundles Are Formed through Progressive Steps Orchestrated by Adjacent Connective Tissue Cells during Primary Myogenesis.

Cell Rep 2020 03;30(10):3552-3565.e6

Randall Centre for Cell and Molecular Biophysics, King's College London, Guy's Campus, London SE1 1UL, UK. Electronic address:

Although the factors regulating muscle cell differentiation are well described, we know very little about how differentiating muscle fibers are organized into individual muscle tissue bundles. Disruption of these processes leads to muscle hypoplasia or dysplasia, and replicating these events is vital in tissue engineering approaches. We describe the progressive cellular events that orchestrate the formation of individual limb muscle bundles and directly demonstrate the role of the connective tissue cells that surround muscle precursors in controlling these events. Read More

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Asymptomatic phaeochromocytoma in a patient with Holt-Oram syndrome: a case report.

Eur Heart J Case Rep 2019 Dec 9;3(4):1-5. Epub 2019 Nov 9.

National University Health System, 5 Lower Kent Ridge Road, Singapore 119074, Singapore.

Background: Holt-Oram syndrome (HOS) is a rare congenital disease that affects the heart and upper limbs. Phaeochromocytoma, a catecholamine-secreting tumour, is a rare neuroendocrine disorder. We present an interesting case presentation of these two rare disorders in a patient who was asymptomatic for phaeochromocytoma. Read More

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December 2019