Ellis-van Creveld syndrome due to a novel EVC2 variant in a patient from Turkey

Mapping Intimacies ◽

10.22541/au.160839989.99464782/v1 ◽

2020 ◽

Author(s):

ÖZDEN ÖZTÜRK ◽

haydar BAĞIŞ ◽

Semih Bolu ◽

Muhammer Özgür Çevik

Keyword(s):

Genetic Analysis ◽

Homozygous Mutation ◽

Cardiac Abnormality ◽

Turkish Child ◽

Ellis Van Creveld Syndrome

Here we report a Turkish child with Ellis-van Creveld syndrome whose presentation was short strature, hypodontia, narrow thorax, dysplastic nails, cardiac abnormality and polydactyly. Genetic analysis revealed novel homozygous mutation in the EVC2 gene (c.3533_3546del). Further research is needed to elucidate the pathophysiological course

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COX deficiency and leukoencephalopathy due to a novel homozygous APOPT1/COA8 mutation

Neurology Genetics ◽

10.1212/nxg.0000000000000464 ◽

2020 ◽

Vol 6 (4) ◽

pp. e464 ◽

Cited By ~ 1

Author(s):

Carola Hedberg-Oldfors ◽

Niklas Darin ◽

Christer Thomsen ◽

Christopher Lindberg ◽

Anders Oldfors

Keyword(s):

Genetic Analysis ◽

Nonsense Mutation ◽

Clinical Investigation ◽

Brain Mri ◽

Homozygous Mutation ◽

Term Outcome ◽

Complex Iv ◽

Long Term Outcome ◽

Long Term Follow Up

ObjectiveTo describe the long-term follow-up and pathogenesis in a child with leukoencephalopathy and cytochrome c oxidase (COX) deficiency due to a novel homozygous nonsense mutation in APOPT1/COA8.MethodsThe patient was clinically investigated at 3, 5, 9, and 25 years of age. Brain MRI, repeat muscle biopsies with biochemical, morphologic, and protein expression analyses were performed, and whole-genome sequencing was used for genetic analysis.ResultsClinical investigation revealed dysarthria, dysphagia, and muscle weakness following pneumonia at age 3 years. There was clinical regression leading to severe loss of ambulation, speech, swallowing, hearing, and vision. The clinical course stabilized after 2.5 years and improved over time. The MRI pattern in the patient demonstrated cavitating leukoencephalopathy, and muscle mitochondrial investigations showed COX deficiency with loss of complex IV subunits and ultrastructural abnormalities. Genetic analysis revealed a novel homozygous mutation in the APOPT1/COA8 gene, c.310T>C; p.(Gln104*).ConclusionsWe describe a novel nonsense mutation in APOPT1/COA8 and provide additional experimental evidence for a COX assembly defect in human muscle causing the complex IV deficiency. The long-term outcome of the disease seems in general to be favorable, and the characteristic MRI pattern with cavitating leukoencephalopathy in combination with COX deficiency should prompt for testing of the APOPT1/COA8 gene.

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SUN-275 A Rare Mutation in the TBX19 Gene Leading to Isolated ACTH Deficiency in Two Siblings

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.283 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Norbert Albers ◽

Amelie Bartels ◽

Renate Peters ◽

Jens Banzer

Keyword(s):

Genetic Analysis ◽

Neonatal Period ◽

Stop Codon ◽

Correct Diagnosis ◽

Premature Stop Codon ◽

Rare Condition ◽

Homozygous Mutation ◽

Upper Respiratory Tract ◽

Isolated Acth Deficiency ◽

Acth Deficiency

Abstract Hypoglycemia and hyperammonemia (>500µg/dl) in a newborn led to the suspicion of THAN (transient hyperammonemia of the newborn). Subsequently, hypoglycemic and salt losing episodes with low cortisol (<0,1 ug/dl) and ACTH (<0,16 pg/ml) levels pointed to ACTH deficiency. Genetic analysis showed a homozygous mutation c.302G>A for p.(Trp101*) in the TBX19 gene (a positive regulator of the transcription of POMC and the terminal differentiation of the corticotrophs), generating a premature stop codon. This mutation has been described only once and very recently by Abali et al (Hormones 18:229; 2019) in a 4 year old girl, but unlike our patients, this girl was obviously unaffected during her neonatal period. All other pituitary axes in our patient were normal, thus congenital isolated ACTH deficiency was the final diagnosis. Hyperammonemia resolved spontaneously and the suspected diagnosis of THAN could be dismissed. Hyperammonemia had probably been due to metabolic stress.After 16 months, a younger brother was born and showed hypoglycemia, hypotension and respiratory infection during his neonatal period. Cortisol and ACTH levels were also very low, thereafter, the same TBX19 mutation was detected.Both brothers were successfully treated with oral hydrocortisone substitution (6–10 mg/sqm/day q8 with increases during stress) and thrive well, except for several infections of the upper respiratory tract in the younger brother. In summary, we report the very rare condition of familial isolated congenital ACTH deficiency with a mutation of TBX19 that has never been described in newborns. Initial presentation may be accompanied by confounding pathological lab findings, while genetic analysis together with extremely low ACTH and cortisol levels confirm the correct diagnosis.

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Identification of Novel Mutations inABCA4Gene: Clinical and Genetic Analysis of Indian Patients with Stargardt Disease

BioMed Research International ◽

10.1155/2015/940864 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 11

Author(s):

Rajani Battu ◽

Anshuman Verma ◽

Ramesh Hariharan ◽

Shuba Krishna ◽

Ravi Kiran ◽

...

Keyword(s):

Genetic Analysis ◽

Vision Loss ◽

Variant Calling ◽

Signs And Symptoms ◽

Cost Effective ◽

Compound Heterozygous ◽

Homozygous Mutation ◽

Stargardt Disease ◽

Indian Patients ◽

Targeted Gene Sequencing

Stargardt disease (STGD) is the leading cause of juvenile macular degeneration associated with progressive central vision loss, photophobia, and colour vision abnormalities. In this study, we have described the clinical and genetic features of Stargardt patients from an Indian cohort. The next generation sequencing was carried out in five clinically confirmed unrelated patients and their family members using a gene panel comprising 184 retinal specific genes. Sequencing results were analyzed by read mapping and variant calling in genes of interest, followed by their verification and interpretation. Genetic analysis revealedABCA4mutations in all of the five unrelated patients. Among these, four patients were found with compound heterozygous mutations and another one had homozygous mutation. All the affected individuals showed signs and symptoms consistent with the disease phenotype. We report two novelABCA4mutations in Indian patients with STGD disease, which expands the existing spectrum of disease-causing variants and the understanding of phenotypic and genotypic correlations. Screening for causative mutations in patients with STGD using panel of targeted gene sequencing by NGS would be a cost effective tool, might be helpful in confirming the precise diagnosis, and contributes towards the genetic counselling of asymptomatic carriers and isolated patients.

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Novel Genetic Findings in a Chinese Family with Axenfeld-Rieger Syndrome

Journal of Ophthalmology ◽

10.1155/2017/5078079 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 7

Author(s):

Kuanshu Li ◽

Liu Yang ◽

Ying Liu ◽

Ding Lin

Keyword(s):

Genetic Counseling ◽

Genetic Analysis ◽

Gene Mutation ◽

Genomic Dna ◽

Gene Mutations ◽

Chinese Family ◽

Heterozygous Mutation ◽

Homozygous Mutation ◽

Specific Therapy ◽

Rieger Syndrome

Purpose. To describe a Chinese family with Axenfeld-Rieger syndrome (ARS) and report our novel genetic findings.Methods. Nine members of the same family underwent complete ophthalmologic examinations and genetic analysis. Genomic DNA was isolated from veinal blood and amplifed using PCR; the products of PCR were sequenced and compared with FOXC1 and PITX2 genes, from which the mutations were found.Results. Through the ophthalmologic examinations, 8 subjects were diagnosed as ARS and 1 subject was normal. A homozygous mutation c.1139_1141dupGCG(p.Gly380_Ala381insGly) and a heterozygous mutation c.1359_1361dupCGG(p.Gly456_Gln457insGly) in FOXC1 were identified in all subjects. The mutation (c.-10-30T>C) was identified in PITX2 in subjects III-1 and III-3.Conclusions.We found novel gene mutations in a Chinese family with ARS, which provides us with a better understanding of the gene mutation spectrum of ARS and the assistance for the genetic counseling and gene-specific therapy in the future.

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A homozygous mutation in a Chinese man with Crigler–Najjar syndrome type II and a family genetic analysis

Journal of Digestive Diseases ◽

10.1111/j.1751-2980.2008.00328.x ◽

2008 ◽

Vol 9 (2) ◽

pp. 89-94 ◽

Cited By ~ 2

Author(s):

Jian Xin WU ◽

Guang Yu CHENG ◽

Jian HUANG

Keyword(s):

Genetic Analysis ◽

Homozygous Mutation ◽

Syndrome Type ◽

Type Ii

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Aldosterone synthase deficiency type II: an unusual presentation of the first Greek case reported with confirmed genetic analysis

Endocrine Regulations ◽

10.2478/enr-2020-0025 ◽

2020 ◽

Vol 54 (3) ◽

pp. 227-229

Author(s):

Stayroula Papailiou ◽

Elpis Athina Vlachopapadopoulou ◽

Amalia Sertedaki ◽

Despoina Maritsi ◽

Nikolaos Syggelos ◽

...

Keyword(s):

Genetic Analysis ◽

Gene Mutations ◽

Failure To Thrive ◽

Homozygous Mutation ◽

Type Ii ◽

Inherited Disease ◽

Aldosterone Synthase ◽

Hormonal Profile ◽

Life Threatening ◽

Aldosterone Synthase Deficiency

AbstractObjective. Aldosterone synthase deficiency (ASD) is a rare, autosomal recessive inherited disease with an overall clinical phenotype of failure to thrive, vomiting, severe dehydration, hyperkalemia, and hyponatremia. Mutations in the CYP11B2 gene encoding aldosterone synthase are responsible for the occurrence of ASD. Defects in CYP11B2 gene have only been reported in a limited number of cases worldwide. Due to this potential life-threatening risk, comprehensive hormonal investigation followed by genetic confirmation is essential for the clinical management of offsprings.Case presentation. We herein describe an unusual case of ASD type II in a neonate with faltering growth as a single presenting symptom. To our knowledge, this is the first Greek case of ASD type II reported with confirmed genetic analysis. Next generation sequencing of her DNA revealed the homozygous mutation p.T185I (ACC-ATC) (c.554C>T) (g.7757C>T) in exon 3 of the CYP11B2 gene in the neonate, inherited from both parents who were heterozygotes for the mutation.Conclusions. Physicians handling neonates with faltering growth, particularly in the initial six weeks of life, should be suspicious of mineralocorticoid insufficiency either as isolated hypoaldosteronism or in the context of congenital adrenal hyperplasia. Essential investigations should be performed and appropriate treatment should be administered promptly without awaiting for the hormonal profile results. Interpretation of the clinical picture and the hormonal profile will guide the analysis of candidate genes. Primary selective hypoaldosteronism is a rare, life threatening disease, but still with an unknown overall population impact. Thus, reporting cases with confirmed gene mutations is of major importance.

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Report of Two Siblings with Overlapping Features of Ellis-van Creveld and Weyers Acrodental Dysostosis

Journal of Clinical Imaging Science ◽

10.4103/2156-7514.95432 ◽

2012 ◽

Vol 2 ◽

pp. 18 ◽

Cited By ~ 1

Author(s):

Devi C. Shetty ◽

Harkanwal P. Singh ◽

Prince Kumar ◽

Chanchal Verma

Keyword(s):

Genetic Analysis ◽

Skeletal Dysplasias ◽

Postaxial Polydactyly ◽

Heterogenous Group ◽

Chromosome 4P16 ◽

Ellis Van Creveld Syndrome ◽

Mode Of Inheritance

Skeletal dysplasias are a heterogenous group of disorders combining abnormalities in the skull and other skeletal bones. Weyers acrofacial dysostosis also known as Weyers acrodental dysostosis was first described in 1952, by Weyers, as a postaxial polydactyly, which had features distinct from, yet some in common with the Ellis-van Creveld Syndrome (EvC). Both the syndromes have been mapped to the same chromosome, 4p16. The cases reported here highlight the overlapping features of both syndromes, which are dissimilar in mode of inheritance and phenotypic severity, emphasizing the need for genetic analysis, to categorize these conditions.

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Phenotypic and genetic analysis of dysprothrombinemia due to a novel homozygous mutation

Hematology ◽

10.1080/10245332.2017.1287332 ◽

2017 ◽

Vol 22 (6) ◽

pp. 380-385 ◽

Cited By ~ 2

Author(s):

Kankan Su ◽

Yanhui Jin ◽

Zhihai Miao ◽

Xiaoli Cheng ◽

Lihong Yang ◽

...

Keyword(s):

Genetic Analysis ◽

Homozygous Mutation

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Molecular and Genetic Analysis of Two Patients with Bernard-Soulier Syndrome – Identification of New Mutations in Glycoprotein Ibα Gene

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656111 ◽

1997 ◽

Vol 77 (06) ◽

pp. 1055-1061 ◽

Cited By ~ 22

Author(s):

Taisuke Kanaji ◽

Takashi Okamura ◽

Mika Kuroiwa ◽

Masaaki Noda ◽

Kingo L Fujimura ◽

...

Keyword(s):

Genetic Analysis ◽

Pcr Amplification ◽

Platelet Membrane ◽

Homozygous Mutation ◽

Immunoblotting Analysis ◽

Mutant Proteins ◽

Single Base ◽

Flow Cytometric ◽

Bernard Soulier Syndrome ◽

New Mutations

SummaryWe investigated two unrelated patients with Bernard-Soulier syndrome (BSS) by performing molecular and genetic analysis.A flow cytometric and immunoblotting analysis showed GP Ibα to be absent from the platelet membrane of both patients. Other glycoproteins that formed GP Ib/IX/V complex were present on the platelets, but in decreased amounts. Therefore, GP Ibα gene from both cases was sequenced after PCR amplification and subcloning. We identified a homozygous mutation of a dinucleotide deletion within the TGTG repeat at cDNA number 972 to 975 in GP Ibα gene from Case 1. In Case 2, compound heterozygosity was demonstrated in GP Ibα gene; an insertion of a single base (T) at cDNA number 1,418 in one allele, and a deletion of a single base (A) within the 7-adenine repeat at cDNA number 1,438 to 1,444 in another allele. The three new mutations in both patients appeared to cause a frameshift, which created a new termination codon shortly thereafter, and thus lead to a GP Ibα deficiency on the platelet membrane. Truncated mutant proteins could be detected in the plasma and platelets of Case 2, but not of Case 1. According to these findings, it is thus supposed that the properties and conformation of additional COOH-terminal peptides, which were supposedly synthesized as results of the mutations, may have an important role on the processing of mutant GP Ibα in megakaryocytes and platelets.

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