scholarly journals Severe Generalized Epidermolysis Bullosa Simplex in Two Hong Kong Children due to De Novo Variants in KRT14 and KRT5

2020 ◽  
Vol 2020 ◽  
pp. 1-5 ◽  
Author(s):  
Shuk Ching Chong ◽  
Kam Lun Hon ◽  
Fernando Scaglia ◽  
Chung Mo Chow ◽  
Yu Ming Fu ◽  
...  
Keyword(s):  
Hong Kong ◽  
Epidermolysis Bullosa ◽  
De Novo ◽  
Genetic Diagnosis ◽  
Recurrence Risk ◽  
Severe Form ◽  
Epidermolysis Bullosa Simplex ◽  
First Case ◽  
Heterozygous Variant ◽  
History Of

We report two Hong Kong children with severe generalized epidermolysis bullosa simplex (EBS), the most severe form of EBS, without a family history of EBS. EBS is a rare genodermatosis usually inherited in an autosomal dominant fashion although rare autosomal recessive cases have been reported. Genetic studies in these patients showed that the first case was due to a novel de novo heterozygous variant, c.377T>G (NM_000526.5 (c.377T>G, p.Leu126Arg)) in the KRT14 gene and the second case was due to a rare de novo heterozygous variant c.527A>G (NM_000424.4, c.527A>G, p.Asn176Ser) in the KRT5 gene. To our knowledge, the c.377T>G variant in the KRT14 gene has not been previously reported, and the c.527A>G variant in the KRT5 gene is a rare cause of severe generalized EBS. In severe generalized EBS, infants exhibit severe symptoms at the onset; however, they tend to improve with time. A precise genetic diagnosis in these two cases aided in counseling the families concerning the prognosis in their affected children and the recurrence risk for future pregnancies.

scholarly journals Identification of a de novo mutation in KRT5 gene underlying epidermolysis bullosa simplex by whole exome sequencing in a Vietnamese patient

2021 ◽  
Vol 19 (2) ◽  
pp. 223-228
Author(s):  
Ma Thi Huyen Thuong ◽  
Dang Tien Truong ◽  
Nguyen Hai Ha ◽  
Nguyen Dang Ton
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Epidermolysis Bullosa ◽  
De Novo ◽  
Recurrence Risk ◽  
Pathogenic Mutation ◽  
De Novo Mutation ◽  
Causative Mutation ◽  
Epidermolysis Bullosa Simplex ◽  
Whole Exome

Epidermolysis bullosa simplex (EBS) is a group of epidermolysis bullosa (EB) and accounts for 75-85% EB cases. Most EBS patients are caused by mutations in KRT5 or KRT14, encoding for keratin 5 and keratin 14, respectively, which impair the structural entirety of paired intermediate filaments expressed in the fracture of basal keratinocytes and subsequent blistering of the epithelium. This study aimed to identify the causative mutation in a Vietnamese EB case. Whole exome sequencing (WES) was performed in the affected individual and revealed a de novo heterozygous pathogenic mutation in exon 7 of KRT5 gene, resulting in an amino acid change at position 477, with glutamic acid to lysine substitution (p.E477K). The KRT5 p.E477K was strong associated with the very severe or lethal of generalized severe EBS (GS-EBS), characterized by the severe symptoms at birth, improving with age and evolution to palmoplantar keratoderma and nail dysplasia. Our finding will aid the molecular diagnosis, prognosis prediction of the patient with GS-EBS due to p.E477K and significant genetic counselling the family concerning the recurrence risk for future pregnancies.

scholarly journals The rare hemoglobin variant Hb Mizuho: report of a Swiss family and literature review

2021 ◽  
Author(s):  
Linet Njue ◽  
Cesare Medri ◽  
Peter Keller ◽  
Miriam Diepold ◽  
Behrouz Mansouri Taleghani ◽  
...  
Keyword(s):  
Literature Review ◽  
Hemolytic Anemia ◽  
De Novo ◽  
Clinical History ◽  
Molecular Techniques ◽  
De Novo Mutation ◽  
First Case ◽  
History Of ◽  
Transfusion Dependency ◽  
Unstable Hemoglobin

AbstractHb Mizuho is a very rare unstable hemoglobin; here, we describe the clinical history of three Swiss family members with Hb Mizuho together with a systematic review of the previously six published cases. The clinical history of the adult woman we report here is unique since this is the first Hb Mizuho presenting with Moyamoya complications and the first case reported with long-term erythrocyte exchange. The literature review showed that Hb Mizuho was mainly reported as a de novo mutation, with the exception of children descended from known cases. All published patients with this unstable hemoglobin showed severe hemolytic anemia with the exception of one; all were regularly transfused. Patients with higher HbF levels might require fewer transfusions. All patients underwent splenectomy at a median age of 4 years and had variable clinical improvement; some achieved complete resolution of transfusion dependency after splenectomy. Iron overload in Hb Mizuho patients seems to be mainly attributed to transfusions and has less to do with ineffective erythropoiesis. Diagnosis might be challenging; a normal hemoglobin electrophoresis should not rule out the diagnosis of unstable hemoglobin in patients with otherwise unexplained hemolytic anemia. This series shows the enormous utility of using molecular techniques for diagnosis.

scholarly journals A de novo mutation in KRT5 in a crossbred calf with epidermolysis bullosa simplex

2020 ◽  
Vol 34 (6) ◽  
pp. 2800-2807
Author(s):  
Joana G. P. Jacinto ◽  
Irene M. Häfliger ◽  
Inês M. B. Veiga ◽  
Cord Drögemüller ◽  
Jørgen S. Agerholm
Keyword(s):  
Epidermolysis Bullosa ◽  
De Novo ◽  
De Novo Mutation ◽  
Epidermolysis Bullosa Simplex

Plectin deficient epidermolysis bullosa simplex with 27-year-history of muscular dystrophy

2005 ◽  
Vol 37 (2) ◽  
pp. 87-93 ◽  
Author(s):  
Yoshie Takahashi ◽  
Fatima Rouan ◽  
Jouni Uitto ◽  
Akemi Ishida-Yamamoto ◽  
Hajime Iizuka ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Epidermolysis Bullosa ◽  
Epidermolysis Bullosa Simplex ◽  
History Of

scholarly journals A Site-Specific Plectin Mutation Causes Dominant Epidermolysis Bullosa Simplex Ogna: Two Identical De Novo Mutations

2002 ◽  
Vol 118 (1) ◽  
pp. 87-93 ◽  
Author(s):  
Dörte Koss-Harnes ◽  
Bjørn Høyheim ◽  
Ingrun Anton-Lamprecht ◽  
Aud. Gjesti ◽  
Randi S. Jørgensen ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
De Novo ◽  
De Novo Mutations ◽  
Epidermolysis Bullosa Simplex ◽  
Site Specific ◽  
A Site

scholarly journals PAX2 Mutation-Related Oligomeganephronia in a Young Adult Patient

2020 ◽  
Vol 10 (3) ◽  
pp. 163-173
Author(s):  
László Bitó ◽  
Tibor Kalmár ◽  
Zoltán Maróti ◽  
Sándor Turkevi-Nagy ◽  
Csaba Bereczki ◽  
...  
Keyword(s):  
English Language ◽  
De Novo ◽  
Enzyme Inhibitor ◽  
Genetic Diagnosis ◽  
Healthy Weight ◽  
Young Adult Patient ◽  
Normal Mean ◽  
History Of ◽  
Compensatory Enlargement ◽  
End Stage

Oligomeganephronic hypoplasia, commonly referred to as oligomeganephronia (OMN), is a rare pediatric disorder characterized by small kidneys. Histologically a paucity of nephrons is observed which show compensatory enlargement. Hyperfiltration injury leads to end-stage kidney disease. Here we report a 23-year-old Caucasian female patient who presented with a 7-year history of nonnephrotic proteinuria, slow worsening of renal function, normal-sized kidneys, normal blood pressure, healthy weight, and normoglycemia. Evaluation of a kidney biopsy specimen revealed sparsely distributed and markedly enlarged glomeruli (glomerular density 0.63/mm<sup>2</sup>, glomerular diameter 268 µm), focal segmental glomerulosclerosis (FSGS), and 70% effacement of the foot processes. The glomerular basement membrane was normal (mean thickness 285 nm). The genetic analysis of 19 genes known to cause FSGS identified a heterozygous de novo nonsense mutation of <i>PAX2</i> in exon 4 (NM_003990.3:c.430C&#x3e;T and NP_003981.2:p.Gln144Ter). Clinical investigations ruled out optic nerve coloboma, hearing loss, and vesicoureteral reflux. Magnetic resonance imaging of the urogenital tract found the uterus to be bicornuate. Based on these data, OMN in nonhypoplastic kidneys and adaptive FSGS related to <i>PAX2</i> mutation was diagnosed. Her kidney function worsened during the 30-month follow-up (last visit: eGFR-EPI 32 mL/min/1.73 m<sup>2</sup>) despite angiotensin-converting enzyme inhibitor treatment. To our best knowledge, our patient is the seventh in the English-language literature with a biopsy diagnosis of OMN in an adult, the first observed with normal-sized kidneys, and the first in whom a specific etiologic genetic diagnosis was established. Nonsense <i>PAX2</i> mutations between the paired domain and the octapeptide domain appear to manifest in renal-limited phenotype.

scholarly journals ‘Isolated’ germline mosaicism in the phenotypically normal father of a girl with X-linked hypophosphatemic rickets

2020 ◽  
Vol 182 (1) ◽  
pp. K1-K6 ◽  
Author(s):  
Yunting Lin ◽  
Yanna Cai ◽  
Jianan Xu ◽  
Chunhua Zeng ◽  
Huiying Sheng ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
De Novo ◽  
Hypophosphatemic Rickets ◽  
Dominant Inheritance ◽  
Germline Mosaicism ◽  
Pathogenic Variants ◽  
First Case ◽  
Heterozygous Variant ◽  
The Family ◽  
Normal Father

Objective X-linked hypophosphatemic rickets (XLHR) is the most common form of inherited rickets caused by pathogenic variants of PHEX gene with an X-linked dominant inheritance pattern. Precise molecular diagnosis of pathogenic variant will benefit the genetic counseling and prenatal diagnosis for the family with XLHR. Here, we presented an ‘isolated’ germline mosaicism in the phenotypically normal father of a girl with XLHR. Methods and results For the initial molecular screen of PHEX gene, DNA samples of the proband and her parents were extracted from their peripheral blood samples respectively. Sanger sequencing found a ‘de novo’ novel heterozygous variant, c.1666C>T(p.Q556X), at the PHEX gene in the proband, but not in her phenotypically healthy parents. Due to an occasional abnormality of his serum phosphate previously, further examinations for the father were taken to exclude the possibility of paternal mosaicism. Eight samples from different tissues were analyzed for PHEX gene by Sanger sequencing. Surprisingly, one ‘isolated’ germline mosaicism was detected only in his sperm with an estimated frequency of 26.67%. The mosaic allele was identical to the c.1666C>T(p.Q556X) variant in the proband. Conclusions This is the first case of ‘isolated’ germline mosaicism with pathogenic PHEX variant. Our study provides accurate diagnosis and valuable counseling for this family. This report also alerts clinicians and geneticists to exclude the possibility of the isolated germline mosaicism and prevent intrafamilial recurrences of inherited diseases.

scholarly journals Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations

2010 ◽  
Vol 162 (5) ◽  
pp. 987-992 ◽  
Author(s):  
S E Flanagan ◽  
R R Kapoor ◽  
G Mali ◽  
D Cody ◽  
N Murphy ◽  
...  
Keyword(s):  
Family History ◽  
De Novo ◽  
Clinical Phenotype ◽  
Mutation Screening ◽  
Genetic Diagnosis ◽  
Gene Mutations ◽  
Hyperinsulinemic Hypoglycemia ◽  
Neonatal Hypoglycemia ◽  
Family History Of Diabetes ◽  
History Of

ObjectiveThe phenotype associated with heterozygous HNF4A gene mutations has recently been extended to include diazoxide responsive neonatal hypoglycemia in addition to maturity-onset diabetes of the young (MODY). To date, mutation screening has been limited to patients with a family history consistent with MODY. In this study, we investigated the prevalence of HNF4A mutations in a large cohort of patients with diazoxide responsive hyperinsulinemic hypoglycemia (HH).Subjects and methodsWe sequenced the ABCC8, KCNJ11, GCK, GLUD1, and/or HNF4A genes in 220 patients with HH responsive to diazoxide. The order of genetic testing was dependent upon the clinical phenotype.ResultsA genetic diagnosis was possible for 59/220 (27%) patients. KATP channel mutations were most common (15%) followed by GLUD1 mutations causing hyperinsulinism with hyperammonemia (5.9%), and HNF4A mutations (5%). Seven of the 11 probands with a heterozygous HNF4A mutation did not have a parent affected with diabetes, and four de novo mutations were confirmed. These patients were diagnosed with HI within the first week of life (median age 1 day), and they had increased birth weight (median +2.4 SDS). The duration of diazoxide treatment ranged from 3 months to ongoing at 8 years.ConclusionsIn this large series, HNF4A mutations are the third most common cause of diazoxide responsive HH. We recommend that HNF4A sequencing is considered in all patients with diazoxide responsive HH diagnosed in the first week of life irrespective of a family history of diabetes, once KATP channel mutations have been excluded.

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