scholarly journals A novel SRY pathogenic variant from a 46,XY female harboring a nonsense point mutation (G to A) in position 293

2021 ◽  
Vol 9 (8) ◽  
Author(s):  
Shengfang Qin ◽  
Xueyan Wang ◽  
Yunxing Li
Keyword(s):  
Point Mutation ◽  
Pathogenic Variant ◽  
Xy Female

scholarly journals A Novel SRY Pathogenic Variant from a 46,XY Female Harboring a Nonsense Point Mutation (G to A) in Position 293

2021 ◽  
Author(s):  
Shengfang Qin ◽  
Xueyan Wang ◽  
Yunxing Li
Keyword(s):  
Point Mutation ◽  
Gene Mutation ◽  
Molecular Diagnosis ◽  
Novel Mutation ◽  
Pathogenic Variant ◽  
Sry Gene ◽  
Pathogenic Role ◽  
Common Cause ◽  
Xy Female

SRY gene mutation is a common cause of 46,XY female. We report a 46,XY female with a novel mutation of SRY c.293G>A (p.Trp98ter). Our report provides evidence for a pathogenic role of the SRY gene c.293G>A mutation in an individual and enlarges the spectrum of molecular diagnosis for these patients.

Paris I Dysfibrinogenemia: A Point Mutation in Intron 8 Results in Insertion of a 15 Amino Acid Sequence in the Fibrinogen γ-Chain

1993 ◽  
Vol 69 (03) ◽  
pp. 217-220 ◽  
Author(s):  
Jonathan B Rosenberg ◽  
Peter J Newman ◽  
Michael W Mosesson ◽  
Marie-Claude Guillin ◽  
David L Amrani
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Point Mutation ◽  
Genomic Dna ◽  
Comparative Sequence Analysis ◽  
Chain Gene ◽  
Molecular Defect ◽  
Nucleotide Position ◽  
Normal Individuals ◽  
Polymerase Chain

SummaryParis I dysfibrinogenemia results in the production of a fibrinogen molecule containing a functionally abnormal γ-chain. We determined the basis of the molecular defect using polymerase chain reaction (PCR) to amplify the γ-chain region of the Paris I subject’s genomic DNA. Comparative sequence analysis of cloned PCR segments of normal and Paris I genomic DNA revealed only an A→G point mutation occurring at nucleotide position 6588 within intron 8 of the Paris I γ-chain gene. We examined six normal individuals and found only normal sequence in this region, indicating that this change is not likely to represent a normal polymorphism. This nucleotide change leads to a 45 bp fragment being inserted between exons 8 and 9 in the mature γparis I chain mRNA, and encodes a 15 amino acid insert after γ350 [M-C-G-E-A-L-P-M-L-K-D-P-C-Y]. Alternative splicing of this region from intron 8 into the mature Paris I γ-chain mRNA also results after translation into a substitution of S for G at position γ351. Biochemical studies of 14C-iodoacetamide incorporation into disulfide-reduced Paris I and normal fibrinogen corroborated the molecular biologic predictions that two additional cysteine residues exist within the γpariS I chain. We conclude that the insertion of this amino acid sequence leads to a conformationallyaltered, and dysfunctional γ-chain in Paris I fibrinogen.

Skeletal and bone material phenotype in recessive osteogenesis imperfecta due to a novel homozygous point mutation in TMEM38B

2015 ◽  
Author(s):  
Emma Webb ◽  
Meena Balasubramanian ◽  
Trevor Cole ◽  
Sue Stewart ◽  
Nicola Crabtree ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Point Mutation ◽  
Bone Material

An audit and insights from clinical exome sequencing in psychiatry: genotype-phenotype correlation

2020 ◽  
Author(s):  
Jayant Mahadevan ◽  
Reeteka Sud ◽  
Ravi Kumar Nadella ◽  
Vani P ◽  
Anand G Subramaniam ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Psychiatric Symptoms ◽  
Pathogenic Variant ◽  
Clinical Exome Sequencing ◽  
Mapt Gene ◽  
Nf1 Gene ◽  
Novel Variant ◽  
History Of ◽  
Atypical Presentations ◽  
Minor Physical Anomalies

BACKGROUND:Psychiatric syndromes have polymorphic symptomatology, and are known to be heritable. Psychiatric symptoms (and even syndromes) often occur as part of the clinical presentation in rare Mendelian syndromes. Clinical exome sequencing reports may help with refining diagnosis and influence treatment decisions, in addition to providing a window into the biology of brain and behaviour. We describe a clinical audit of 12 individuals who sought treatment at our hospital, and for whom targeted sequencing was ordered. Three cases are discussed in detail to demonstrate correlations between genotype and phenotype in the clinic.METHODS:Targeted Next-Generation Sequencing (NGS) was done using Clinical Exome Panel (TruSight One, Illumina) covering coding exons and flanking intronic sequences of 4811 genes associated with known inherited diseases. Variants detected were classified according to the American College for Medical Genetics (ACMG) recommendation for standards of interpretation and reporting of sequence variations.RESULTS:Ten out of twelve cases had at least one pathogenic variant. In one of these cases, we detected a known pathogenic variant in MAPT gene in a suspected FTD case, which helped us to confirm the diagnosis. In another case, we detected a novel variant predicted to be deleterious in NF1 gene. Identification of this mutation suggested a change in treatment for the patient, that was of benefit. The same patient also harboured a novel variant in the TRIO gene. This gene may be involved in biological processes that underlie the patient’s psychiatric illness.CONCLUSIONS:The cases discussed here exemplify different scenarios under which targeted exome sequencing can find meaningful application in the clinic: confirming diagnosis (MAPT variant), or modifying treatment (NF1). We suggest that clinical exome sequencing can be a helpful addition to a clinician’s toolkit when there are expediting factors to consider— such as early-onset, strong family history of mental illness, complex/atypical presentations and minor physical anomalies or neurocutaneous markers.

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