scholarly journals Identification of a Novel Mutation in a Family with Pseudohypoparathyroidism Type 1a

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Adelaide Moutinho ◽  
Rosa Carvalho ◽  
Rita Ferreira Reis ◽  
Sandra Tavares
Keyword(s):  
Autosomal Dominant ◽  
Clinical Phenotype ◽  
Novel Mutation ◽  
Target Organ ◽  
Heterozygous Mutation ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
The Family ◽  
Gnas Gene ◽  
Gnas Mutation

Introduction. Pseudohypoparathyroidism type 1a is caused by GNAS mutations leading to target organ resistance to multiple hormones rather than parathyroid hormone, resulting not only in hypocalcemia, but also in Albright’s hereditary osteodystrophy phenotype. Materials and Methods. DNA sequencing of the GNAS gene identified a novel heterozygous mutation in peripheral blood leukocytes in the family presented in this case report. Results. We present a case of a 25-year-old woman with pseudohypoparathyroidism type 1a admitted with seizures, whose family presents an autosomal dominant transmission of a novel heterozygous GNAS mutation (c.524_530+3del). Conclusion. Pseudohypoparathyroidism type 1a is mostly caused by inactivating GNAS mutations that have been gradually reported in the literature that lead to a typical and complex clinical phenotype and resistance to multiple hormones. The deletion caused by the mutation identified in the presented case has not been reported previously.

scholarly journals A novel mutation in the ACAN gene in a family with autosomal dominant short stature and intervertebral disc disease

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Noboru Uchida ◽  
Hironori Shibata ◽  
Gen Nishimura ◽  
Tomonobu Hasegawa
Keyword(s):  
Intervertebral Disc ◽  
Short Stature ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Bone Age ◽  
Heterozygous Mutation ◽  
Intervertebral Disc Disease ◽  
Disc Disease ◽  
The Family ◽  
Old Japanese

AbstractHeterozygous mutations in the ACAN gene have been reported in individuals with short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans. We report a family with a phenotypic constellation carrying a novel mutation in the ACAN gene. The proband was a 7-year-old Japanese girl with short stature. Her mother and maternal grandmother also had short stature and intervertebral disc disease. We analyzed the ACAN gene in the family and identified a novel heterozygous mutation: c.4634delT, Leu1545Profs*11.

scholarly journals A family study of congenital dysfibrinogenemia caused by a novel mutation in the FGA gene: A case report

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 769-773
Author(s):  
Yingli Qiao ◽  
Qisi Zhang ◽  
Poshi Xu ◽  
Yuhui Deng
Keyword(s):  
Missense Mutation ◽  
Novel Mutation ◽  
Screening Tests ◽  
Heterozygous Mutation ◽  
Thrombin Time ◽  
Mutation Site ◽  
Functional Activities ◽  
Heterozygous Missense Mutation ◽  
The Family ◽  
A Chain

AbstractCongenital dysfibrinogenemia (CD) is a rare hereditary fibrinogen disorder characterized by normal fibrinogen antigen levels associated with lower functional activities. The aim of this study is to analyze the phenotype and genotype of a family of CD. Routine coagulation screening tests were performed on the proband, her parents, and her grandparents. Then, the purified genomic DNA extracted from peripheral blood was amplified by PCR, and Sanger sequencing was performed to further confirm the mutation. The prothrombin time and activated partial thromboplastin time of the proband were normal, thrombin time prolonged, and the activity of fibrinogen (Fg:Ac) decreased significantly, but fibrinogen antigen (Fg:Ag) level was normal. The coagulation function indices of the proband’s father and grandfather were similar to her, and the indices of her mother and grandmother were normal. Sequencing results showed that the proband had a heterozygous missense mutation in FGA gene c.92G > A, which caused the mutation of amino acid 31 from glycine to glutamic acid (p.Gly31Glu). Her father had the same heterozygous mutation. In conclusion, the proband suffered from CD. The change of Gly31Glu in A chain due to the c.92G > A heterozygous missense mutation in the FGA gene is the cause of CD in the family. To the best of our knowledge, the mutation site is new and first reported so far.

scholarly journals Novel germline mutation (Leu512Met) in the thyrotropin receptor gene (TSHR) leading to sporadic non-autoimmune hyperthyroidism

2017 ◽  
Vol 30 (3) ◽  
Author(s):  
Stephanie A. Roberts ◽  
Jennifer E. Moon ◽  
Andrew Dauber ◽  
Jessica R. Smith
Keyword(s):  
Autosomal Dominant ◽  
De Novo ◽  
Receptor Gene ◽  
De Novo Mutation ◽  
Thyrotropin Receptor ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Activating Mutation ◽  
Neonatal Hyperthyroidism ◽  
Exon 10

AbstractBackground:Primary nonautoimmune hyperthyroidism is a rare cause of neonatal hyperthyroidism. This results from an activating mutation in the thyrotropin-receptor (TSHR). It can be inherited in an autosomal dominant manner or occur sporadically as a de novo mutation. Affected individuals display a wide phenotype from severe neonatal to mild subclinical hyperthyroidism. We describe a 6-month-old boy with a de novo mutation in theMethods:Genomic DNA from the patient’s and parents’ peripheral blood leukocytes was extracted. Exons 9 and 10 of theResults:Sequencing exon 10 of theConclusions:The p.Leu512Met mutation (c.1534C>A) of the

scholarly journals Genotype–phenotype correlation in a family with primary cortisol resistance: possible modulating effect of the ER22/23EK polymorphism.

2008 ◽  
Vol 158 (4) ◽  
pp. 577-582 ◽  
Author(s):  
Hussein Raef ◽  
Essa Y Baitei ◽  
Minjing Zou ◽  
Yufei Shi
Keyword(s):  
Glucocorticoid Receptor ◽  
Partial Resistance ◽  
Genomic Dna ◽  
Clinical Phenotype ◽  
Severe Hypertension ◽  
Family Members ◽  
Heterozygous Mutation ◽  
Phenotype Correlation ◽  
The Family ◽  
Cortisol Suppression

ObjectiveGlucocorticoid resistance is a rare sporadic or familial condition that is characterized by generalized, partial resistance to glucocorticoids. It is caused by a mutation in the glucocorticoid receptor-α (GR-α) gene. We aimed to understand the reasons for different phenotypes (severe to asymptomatic) observed in a family with primary cortisol resistance.DesignThe genotype leading to cortisol resistance in the family members was investigated and correlated to the clinical phenotype.MethodThree siblings were presented with clinical cortisol resistance, featuring severe hypertension, hypokalemia and hyperandrogenism. Three other siblings and both parents were asymptomatic. Genomic DNA from peripheral lymphocytes was isolated from family members. The entire GR-α coding sequence (exons 2–9) was amplified by PCR and sequenced.ResultsA homozygous G679S mutation was present in the three clinically affected subjects. Heterozygous G66A (E22E) and G68A (R23K) polymorphisms and G2035A (G679S) mutation were found in the father and two siblings. Mother and one sibling had only heterozygous G679S mutation. The clinically unaffected subjects showed two different responses to dexamethason. Those with heterozygous G679S mutation and ER22/23EK polymorphism had normal cortisol suppression, whereas those with only heterozygous G679S mutation failed to suppress normally.ConclusionsA homozygous G679S mutation of the GR-α gene is associated with severe cortisol resistance, whereas a heterozygous mutation of the same gene can lead to subclinical cortisol resistance. The effect of the heterozygous mutation was abolished in subjects carrying the ER22/23EK polymorphism.

scholarly journals A familial case of Syndactyly type IV due to a novel duplication of ~222.23 kb covering exons 2-17 of the LMBR1 gene: a case report

2018 ◽  
Author(s):  
Lijing Shi ◽  
Hui Huang ◽  
Qiuxia Jiang ◽  
Rongsen Huang ◽  
Wanyu Fu ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Clinical Phenotype ◽  
Regulatory Element ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Type Iv ◽  
Limb Malformations ◽  
Triphalangeal Thumb ◽  
Generation Sequencing ◽  
Syndactyly Type Iv

ABSTRACTSyndactyly is one of the most frequent hereditary limb malformations with clinical and genetical complexity. Autosomal dominant Syndactyly type IV (SD4) is a very rare form of syndactyly, occurring as a result of heterozygous mutation in an SHH regulatory element (ZRS) that resides in intron 5 of the LMBR1 gene on chromosome 7q36.3. The SD4 is characterized by complete cutaneous syndactyly of all fingers, cup-shaped hands due to flexion of the fingers and accompanied by polydactyly. Here, we firstly reported a big Chinese family, manifesting cup-shaped hands consistent with SD4 and intrafamilial heterogeneity in clinical phenotype of tibial and fibulal shortening, triphalangeal thumb-polysyndactyly syndrome (TPTPS). Genetically, we identified a novel duplication of ∼222.23 kb covering exons 2-17 of the LMBR1 gene in this family by next generation sequencing. This case expands our new clinical understanding of SD4 phenotype.

Sign in / Sign up

Export Citation Format

Share Document