A Novel Mutation of the DHCR7 Gene in a Sicilian Compound Heterozygote with Smith-Lemli-Opitz Syndrome

2005 ◽  
Vol 9 (4) ◽  
pp. 201-204 ◽  
Author(s):  
Fabrizio Romano ◽  
Barbara Fiore ◽  
Franca Maria Pezzino ◽  
Maria Teresa Longombardo ◽  
Angelo Baldassare Cefalù ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Compound Heterozygote ◽  
Opitz Syndrome

Novel mutation in the ?7-dehydrocholesterol reductase gene in an Australian patient with Smith-Lemli-Opitz syndrome

2001 ◽  
Vol 103 (4) ◽  
pp. 344-347 ◽  
Author(s):  
Timothy Evans ◽  
Alisa Poh ◽  
Charlotte Webb ◽  
Brandon Wainwright ◽  
Carol Wicking ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Reductase Gene ◽  
Opitz Syndrome

scholarly journals Heterogeneity of Nuclear Lamin A Mutations in Dunnigan-Type Familial Partial Lipodystrophy*

2000 ◽  
Vol 85 (9) ◽  
pp. 3431-3435
Author(s):  
Robert A. Hegele ◽  
Henian Cao ◽  
Carol M. Anderson ◽  
Irene M. Hramiak
Keyword(s):  
Environmental Factors ◽  
Novel Mutation ◽  
Compound Heterozygote ◽  
Lamin A ◽  
Missense Mutations ◽  
Compound Heterozygosity ◽  
Partial Lipodystrophy ◽  
Nuclear Lamin ◽  
Familial Partial Lipodystrophy ◽  
Affected Subject

Abstract We previously identified a novel mutation, namely LMNA R482Q, that was found to underlie Dunnigan-type partial lipodystrophy (FPLD) and diabetes in an extended Canadian kindred. We have since sequenced LMNA in five additional Canadian FPLD probands and herein report three new rare missense mutations in LMNA: V440M, R482W, and R584H. One severely affected subject was a compound heterozygote for both V440M and R482Q. The findings indicated that 1) a spectrum of LMNA mutations underlies FPLD; 2) aberrant lamin A, and not lamin C, is likely to underlie FPLD, as R584H occurs within LMNA sequence that is specific for lamin A; 3) the V440M mutation may not cause lipodystrophy on its own; 4) compound heterozygosity for V440M and R482Q is associated with a relatively more severe FPLD phenotype, but not with complete lipodystrophy; and 5) variation in the severity of the phenotype might be related to environmental factors.

A patient with Smith–Lemli–Opitz syndrome: novel mutation of the DHCR7 gene and effects of therapy with simvastatin and cholesterol supplement

2009 ◽  
Vol 169 (1) ◽  
pp. 121-123 ◽  
Author(s):  
Gabriella P. Szabó ◽  
Anna V. Oláh ◽  
Libor Kozak ◽  
Erzsébet Balogh ◽  
Andrea Nagy ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Opitz Syndrome

scholarly journals Novel Mutations in the GTPBP3 Gene for Mitochondrial Disease and Characteristics of Related Phenotypic Spectrum: The First Three Cases From China

2021 ◽  
Vol 12 ◽  
Author(s):  
Hui-ming Yan ◽  
Zhi-mei Liu ◽  
Bei Cao ◽  
Victor Wei Zhang ◽  
Yi-duo He ◽  
...  
Keyword(s):  
Mitochondrial Disease ◽  
Chinese Population ◽  
Novel Mutation ◽  
Case Series ◽  
Myocardial Damage ◽  
Compound Heterozygote ◽  
Novel Mutations ◽  
Mild Phenotype ◽  
Phenotypic Spectrum ◽  
Human Mitochondrial Genome

Combined Oxidative Phosphorylation Deficiency 23 (COXPD23) caused by mutations in GTPBP3 gene is a rare mitochondrial disease, and this disorder identified from the Chinese population has not been described thus far. Here, we report a case series of three patients with COXPD23 caused by GTPBP3 mutations, from a severe to a mild phenotype. The main clinical features of these patients include lactic acidosis, myocardial damage, and neurologic symptoms. Whole genome sequencing and targeted panels of candidate human mitochondrial genome revealed that patient 1 was a compound heterozygote with novel mutations c.413C > T (p. A138V) and c.509_510del (p. E170Gfs∗42) in GTPBP3. Patient 2 was a compound heterozygote with novel mutations c.544G > T (p. G182X) and c.785A > C (p.Q262P), while patient 3 was a compound heterozygote with a previously reported mutation c.424G > A (p.E142K) and novel mutation c.785A > C (p.Q262P). In conclusion, we first describe three Chinese individuals with COXPD23, and discuss the genotype-phenotype correlations of GTPBP3 mutations. Our findings provide novel information in the diagnosis and genetic counseling of patients with mitochondrial disease.

Identification and Characterization of a New Mutation in Coagulation Factor VII (Carmel mutation), with Different Reactivity Towards Tissue Factors of Different Origin

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1396-1396
Author(s):  
Aliza Cassel ◽  
Nurit Rosenberg ◽  
Emad Muhammad ◽  
Rima Dazdik ◽  
Miriam Berl ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Novel Mutation ◽  
Direct Sequencing ◽  
Compound Heterozygote ◽  
Factor Vii ◽  
Rabbit Brain ◽  
Molecular Defect ◽  
Bleeding Tendency ◽  
Tissue Factors ◽  
Fvii Deficiency

Abstract Inherited factor VII (FVII) deficiency is a rare autosomal recessive disorder manifested by bleeding tendency in homozygotes or compound heterozygotes. The bleeding tendency is variable and does not always correlate with the measured amount of FVII. More than 30 mutations causing FVII deficiency have been identified. The aim of this study was to identify the molecular defect in a family with FVII abnormality and to characterize the functional defect and its clinical consequences. An 80 year old woman showed various prolonged prothrombin time (PT) dependent on the origin of tissue factors (TF) in the reagents, in the range of 5-18%. FVII activity measured using placenta human TF was ~4% and less than 1% using recombinant human TF or rabbit brain TF. Direct sequencing of PCR-amplified FVII genomic DNA exons demonstrated a single homozygous nucleotide exchange G>A in exon 6 predicting missense mutation Tyr164Cys, in close vicinity to the active site of the protease and to the binding site of FX. Sequencing of exon 6 in six members of the family comprising three generations was performed. All of them exhibited low activity of FVII. Direct sequencing of PCR-amplified exon 6 demonstrated that her son, daughter and grand-daughter are heterozygote to the novel mutation, Tyr164Cys, henceforth, Carmel mutation. The grand -daughter (third generation) was identified as a compound heterozygote carrying in addition an Ala244Val mutation along with a Arg353Gln polymorphism, a well-known linkage previously characterized in the Israeli population, inherited from the paternal side. Her FVII activity was 3-7% and 8% FVII antigen. In the individuals heterozygote for Tyr164Cys we detected 41-54% activity and 46-66% antigenic FVII. The measurement of VIIa in the proband and her grand-daughter could not demonstrate any activity in plasma, possibly because of perturbation of the interaction between the mutated FVII and TF or FX which are part of the assay. The heterozygote for Tyr164Cys showed approximately 30% FVIIa of normal controls . Despite the dramatic laboratory presentation, the clinical manifestation of the Tyr164Cys genotype is very mild, suggesting that a low level of FVII is sufficient to prevent bleeding. The homozygous patient reached an old age, gave birth to two children and did not suffer any major bleedings during her life. The compound heterozygote presents a similar phenotype with slightly higher FVII activity and antigen, no measurable FVIIa activity and mild clinical presentation. Further investigation into this novel mutation is needed in order to characterize the interaction of the FVII with TF, phospholipids and FX and to understand the reason for such low amount of FVII protein in plasma. Disclosures No relevant conflicts of interest to declare.

Canavan disease in compound heterozygote with novel mutation (C913 → A) in aspartoacylase gene

1994 ◽  
Vol 11 (2) ◽  
pp. 145
Author(s):  
E.H. Kolodny ◽  
M.A. Gama Sosa ◽  
E. Leshinsky ◽  
D. Dwyer ◽  
S. Battistini ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Canavan Disease ◽  
Compound Heterozygote

Smith-Lemli-Opitz syndrome: clinical and biochemical correlates

2018 ◽  
Vol 31 (4) ◽  
pp. 451-459 ◽  
Author(s):  
Sarah E. Donoghue ◽  
James J. Pitt ◽  
Avihu Boneh ◽  
Susan M. White
Keyword(s):  
Novel Mutation ◽  
Cholesterol Biosynthesis ◽  
Autosomal Recessive Disorder ◽  
Branchial Arch ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Cholesterol Levels ◽  
Midline Defects ◽  
Opitz Syndrome

AbstractBackground:Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder caused by mutations in theDHCR7gene that result in reduced cholesterol biosynthesis. The aim of the study was to examine the biochemical and clinical features of SLOS in the context of the emerging evidence of the importance of cholesterol in morphogenesis and steroidogenesis.Methods:We retrospectively reviewed the records of 18 patients (including four fetuses) with confirmed SLOS and documented their clinical and biochemical features.Results:Seven patients had branchial arch abnormalities, including micrognathia, immune dysfunction and hypocalcemia. Thymic abnormalities were found in three fetuses. All four patients with a cholesterol level of ≤0.35 mmol/L died. They all had electrolyte abnormalities (hyperkalemia, hyponatremia, hypocalcemia), necrotizing enterocolitis, sepsis-like episodes and midline defects including the branchial and cardiac defects. Patients with cholesterol levels ≥1.7 mmol/L had milder features and were diagnosed at 9 months to 25 years of age. All 10 patients had intellectual disability. One patient was found to have a novel mutation, c.1220A>G (p.Asn407Ser).Conclusions:We suggest that screening for adrenal insufficiency and for hypoparathyroidism, hypothyroidism and immunodeficiency, should be done routinely in infants diagnosed early with SLOS. Early diagnosis and intervention to correct these biochemical consequences may decrease mortality and improve long-term outcome in these patients.

Congenital mirror movements in a family with a novel mutation in the DCC gene

2011 ◽  
Vol 42 (S 01) ◽  
Author(s):  
GC Korenke ◽  
M Wagner ◽  
A Maak ◽  
G Rosenberger ◽  
K Kutsche
Keyword(s):  
Novel Mutation ◽  
Mirror Movements ◽  
Dcc Gene
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