A novel TAB2 mutation detected in a putative case of frontometaphyseal dysplasia

AbstractFrontometaphyseal dysplasia (FMD) type 2 is an autosomal dominant disorder characterized by skeletal abnormalities and caused by MAP3K7 mutation. We identified a novel missense mutation in TAB2 associated with FMD in a child with multiple congenital malformations. This case was diagnosed as FMD due to joint contractures and bone deformities. This is the third report of FMD caused by a TAB2 mutation located in the TAK1-binding region.

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Mild Encephalitis/Encephalopathy with Reversible Splenial Lesion (MERS) due to Acute Intermittent Porphyria with a novel mutation in the porphobinoglien deaminase gene

10.21203/rs.2.19929/v1 ◽

2020 ◽

Author(s):

xiaoqing li ◽

fei han ◽

qianlong chen ◽

tienan zhu ◽

yongqiang zhao ◽

...

Keyword(s):

Autosomal Dominant ◽

Stop Codon ◽

Novel Mutation ◽

Acute Intermittent Porphyria ◽

Porphobilinogen Deaminase ◽

Splicing Mutation ◽

Autosomal Dominant Disorder ◽

The Third ◽

Splenial Lesion ◽

Partial Deficiency

Abstract Background: Mild encephalopathy with a reversible splenial lesion (MERS) is a clinico-radiological syndrome characterized by a reversible isolated lesion with transiently reduced diffusion in the central portion of the splenium of the corpus callosum (SCC). The reason for MERS is unknown. however, infectious-related MERS (in particular virus) remains the most common cause of reversible splenial lesions. Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by a partial deficiency of porphobilinogen deaminase (PBGD), the third enzyme in the of hemebiosynthetic pathway. It can affect the autonomic, peripheral, and central nervous system. Result: In this study, we report a 20-year-old woman with AIP who presented with MR manifestations suggestive of MERS, she had a novel PBGD splicing mutation, a G to A mutation in base 594 resulting in tryptophan to a stop codon (W198*). Conclusion: To the best of our knowledge, this is only one published case of MERS associated with AIP.

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Hypertension and Brachydactyly Syndrome Associated With Vertebral Artery Malformation Caused by a PDE3A Missense Mutation

American Journal of Hypertension ◽

10.1093/ajh/hpz151 ◽

2019 ◽

Author(s):

Peng Fan ◽

Di Zhang ◽

Kun-Qi Yang ◽

Qiong-Yu Zhang ◽

Fang Luo ◽

...

Keyword(s):

Vertebral Artery ◽

Missense Mutation ◽

Autosomal Dominant ◽

Chinese Family ◽

Autosomal Dominant Disorder ◽

Conserved Domain ◽

Long Term Follow Up ◽

Generation Sequencing

Abstract BACKGROUND Hypertension and brachydactyly syndrome (HTNB), also called Bilginturan syndrome, is a rare autosomal dominant disorder characterized by severe salt-independent hypertension, a short stature, brachydactyly, and death from stroke before the age of 50 years when untreated. The purpose of the present study was to identify a PDE3A mutation leading to HTNB associated with vertebral artery malformation in a Chinese family. METHODS Peripheral blood samples were collected from all subjects for DNA extraction. Next-generation sequencing and Sanger sequencing were performed to identify the PDE3A mutation. A comparative overview was performed in the probands with HTNB caused by PDE3A mutations. RESULTS Genetic analysis identified a missense mutation in PDE3A, c.1346G>A, in the proband with HTNB. This mutation, resulting in p.Gly449Asp, was located in a highly conserved domain and predicted to be damaging by different bioinformatics tools. Cosegregation analyses showed that the proband inherited the identified mutation from her father. Antihypertensive therapy was effective for the proband. Comparative overview of HTNB probands with 9 different PDE3A mutations revealed phenotypic heterogeneity. CONCLUSIONS Genetic screening can significantly improve the diagnosis of HTNB patients at an early age. Our study not only adds to the spectrum of PDE3A mutations in the Chinese population and extends the phenotype of HTNB patients to include vertebral malformation but also improves the awareness of pathogenesis in HTNB patients. We emphasize the importance of antihypertensive treatment and long-term follow-up to prevent stroke and adverse cardiovascular events.

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NFB-02. TREATMENT OF PAIN AND TUMOR GROWTH IN NF2

Neuro-Oncology ◽

10.1093/neuonc/noaa222.606 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii418-iii418

Author(s):

Molly Hemenway ◽

Anan Nellan ◽

Kate McMahon ◽

Nicholas Foreman ◽

Kartik Reddy ◽

...

Keyword(s):

Autosomal Dominant ◽

Neurofibromatosis Type ◽

Mek Inhibitor ◽

Pain Medication ◽

Autosomal Dominant Disorder ◽

Medical Visits ◽

Oral Medications

Abstract BACKGROUND Neurofibromatosis Type 2 (NF2) is an autosomal dominant disorder characterized by multiple nervous system tumors. Chronic pain affects the majority of patients with NF2 and is the primary factor that contributes to decreased quality of life. There are limited therapies that effectively reduce pain in NF2, but intravenous (IV) bevacizumab has been reported to provide significant relief to patients suffering from debilitating pain. CASE STUDY James is a 24-year-old who initially presented with manifestations of NF2 at age 10, and by 15 years old had developed daily pain affecting his neck, back, and lower extremity. He has multiple CNS schwannomas, meningiomas, neurofibromas, and meets clinical NF2 criteria. While genetic testing did not reveal a mutation in his gDNA, low level skipping of exon 4 via RNA supports (likely mosaic) NF2. James’s pain was poorly controlled with multiple oral medications, including opioids. James started IV bevacizumab at age 16 that improved his pain. He was critically dependent on bevacizumab for pain control and required continuous IV pain medication when bevacizumab was held for a surgical procedure. Following five years of bevacizumab he developed worsening toxicities including hypertension, proteinuria, and elevated hemoglobin. James transitioned to therapy with trametinib, a MEK inhibitor, and was able to wean off bevacizumab six months later. Treatment of NF2 related pain with trametinib instead of bevacizumab has improved his QOL with decreased medical visits, improved pain management, and decreased side effects. FUTURE IMPLICATIONS: Treatment of NF2 tumor related pain can be managed with MEK inhibitors.

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Cleidocranial Dysplasia: A Case Report

TAJ Journal of Teachers Association ◽

10.3329/taj.v21i2.3799 ◽

1970 ◽

Vol 21 (2) ◽

pp. 166-169

Author(s):

M Azizul Haque ◽

ARM Saifuddin Ekram ◽

M Durrul Huda

Keyword(s):

Case Report ◽

Short Stature ◽

Autosomal Dominant ◽

Cleidocranial Dysplasia ◽

Supernumerary Teeth ◽

Autosomal Dominant Disorder ◽

Skeletal Abnormalities ◽

Wide Range

Cleidocranial dysplasia is an autosomal dominant disorder with a wide range of expression, characterized by clavicular aplasia or hypoplasia, retarded cranial ossification, supernumerary teeth, short stature and a variety of other skeletal abnormalities. We are reporting a case of Cleidocranial dysplasia with literature is review. doi: 10.3329/taj.v21i2.3799 TAJ 2008; 21(2): 166-169

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Familial Juvenile Hyperuricemic Nephropathy and Autosomal Dominant Medullary Cystic Kidney Disease Type 2: Two Facets of the Same Disease?

Journal of the American Society of Nephrology ◽

10.1681/asn.v12112348 ◽

2001 ◽

Vol 12 (11) ◽

pp. 2348-2357 ◽

Cited By ~ 1

Author(s):

KARIN DAHAN ◽

ARNO FUCHSHUBER ◽

STAVROULA ADAMIS ◽

MICHÈLE SMAERS ◽

SABINE KROISS ◽

...

Keyword(s):

Kidney Disease ◽

Autosomal Dominant ◽

Disease Type ◽

Basement Membranes ◽

Cystic Kidney Disease ◽

Cystic Kidney ◽

Autosomal Dominant Disorder ◽

Medullary Cystic Kidney Disease ◽

Familial Juvenile Hyperuricemic Nephropathy

Abstract. Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal dominant disorder heralded by hyperuricemia during childhood; it is characterized by chronic interstitial nephritis, with marked thickening of tubular basement membranes, and leads to progressive renal failure during adulthood. A gene for FJHN in two Czech families was recently mapped to chromosome 16p11.2, close to the MCKD2 locus, which is responsible for a variant of autosomal dominant medullary cystic kidney disease observed in an Italian family. In a large Belgian family with FJHN, a tight linkage between the disorder and the marker D16S3060, located within the MCKD2 locus on chromosome 16p12 (maximal two-point logarithmic odds score of 3.74 at a recombination fraction of θ = 0), was observed in this study. The candidate region was further narrowed to a 1.3-Mb interval between D16S501 and D16S3036. Together with the striking clinical and pathologic resemblance between previously reported medullary cystic kidney disease type 2 and FJHN occurring in the Belgian family (including the presence of medullary cysts), this study suggests that these two disorders are facets of the same disease.

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Brugada syndrome with a novel missense mutation D252N in SCN5A gene: a case report

Ministry of Science and Technology, Vietnam ◽

10.31276/vjst.63(7).01-06 ◽

2021 ◽

Vol 63 (7) ◽

pp. 1-6

Author(s):

Duy Phuong Dang ◽

◽

Minh Ha Nguyen ◽

Doan Loi Do ◽

Van Khanh Tran ◽

...

Keyword(s):

Missense Mutation ◽

Brugada Syndrome ◽

Autosomal Dominant ◽

Clinical Symptoms ◽

Novel Mutation ◽

Ecg Changes ◽

Functional Protein ◽

Conserved Gene ◽

Scn5a Gene

Brugada syndrome is an inherited cardiac arrhythmia that follows autosomal dominant transmission and can cause sudden death. This paper reported a case of Brugada syndrome in a 43-year-old male patient with no clinical symptoms. Brugada-type 2-ECG changes were accidentally detected. Flecainide test was done and proved positive. Gene analysis revealed a novel missense mutation in the SCN5A gene with a genetic variation of D252N. This novel mutation has not been reported on any genetic databases related to Brugada syndrome. Functional protein analysis software suggested that the mutation occurs in the highly conserved gene and probably has a damaging effect. This is the first Brugada syndrome case reported with a mutation in the SCN5A gene in Vietnam.

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Hereditary phlebectasis of the lips. An autosomal dominant disorder

Archives of Dermatology ◽

10.1001/archderm.112.5.712 ◽

1976 ◽

Vol 112 (5) ◽

pp. 712-714

Author(s):

W. B. Reed

Keyword(s):

Autosomal Dominant ◽

Autosomal Dominant Disorder

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A Novel Missense Mutation in the Endoglin Gene in Hereditary Hemorrhagic Telangiectasia

Thrombosis and Haemostasis ◽

10.1055/s-0038-1655946 ◽

1997 ◽

Vol 77 (02) ◽

pp. 243-247 ◽

Cited By ~ 15

Author(s):

Hiroshi Yamaguchi ◽

Hiroyuki Azuma ◽

Toshio Shigekiyo ◽

Hideo Inoue ◽

Shiro Saito

Keyword(s):

Missense Mutation ◽

Hereditary Hemorrhagic Telangiectasia ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Autosomal Dominant Disorder ◽

Her Family ◽

Normal Individuals ◽

Oligonucleotide Hybridization ◽

Vascular Dysplasia ◽

Exon 4

SummaryHereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by multisystem vascular dysplasia and recurrent hemorrhage. Recent investigation has mapped one of the responsible genes for HHT to chromosome 9q33-q34; subsequently, nine different mutations have been identified in the endoglin gene, which encodes a transforming growth factor β(TGF-β) binding protein, in nine unrelated families with HHT. We examined the endoglin gene in a Japanese patient with HHT and her family members. Using PCR-SSCP. analysis followed by sequencing, we identified a C to A missense mutation in exon 4 which changed an Ala160 codon(GCT) to an Asp160 codon (GAT). Since this mutation destroys one of three Fnu4H I sites in exon 4, the Fnu4H I digestion patterns of the PCR-amplified exon 4 fragments from each family member were analyzed. In affected members, the restriction patterns were all consistent with a phenotype of HHT. PCR-amplified exon 4 fragments from 150 normal individuals were also analyzed by allele-specific oligonucleotide hybridization analysis. As a result, the mutation was not found in any of them. We conclude that the C to A mutation in exon 4 of the endoglin gene in this proband is responsible for the occurrence of HHT in this family.

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