scholarly journals Functional and structural characterization of novel mutations and genotype-phenotype correlation in 51 phenylalanine hydroxylase deficient families from Southern Italy

FEBS Journal ◽  
2009 ◽  
Vol 276 (7) ◽  
pp. 2048-2059 ◽  
Author(s):  
Aurora Daniele ◽  
Iris Scala ◽  
Giuseppe Cardillo ◽  
Cinzia Pennino ◽  
Carla Ungaro ◽  
...  
Keyword(s):  
Structural Characterization ◽  
Southern Italy ◽  
Phenylalanine Hydroxylase ◽  
Phenotype Correlation ◽  
Novel Mutations ◽  
Genotype Phenotype Correlation

Structural characterization of the 5' regions of the human phenylalanine hydroxylase gene

Biochemistry ◽  
1992 ◽  
Vol 31 (35) ◽  
pp. 8363-8368 ◽  
Author(s):  
David S. Konecki ◽  
Yibin Wang ◽  
Friedrich K. Trefz ◽  
Uta Lichter-Konecki ◽  
Savio L. C. Woo
Keyword(s):  
Structural Characterization ◽  
Phenylalanine Hydroxylase ◽  
Hydroxylase Gene ◽  
Phenylalanine Hydroxylase Gene ◽  
Human Phenylalanine Hydroxylase

Co-expression of phenylalanine hydroxylase variants and effects of interallelic complementation on in vitro enzyme activity and genotype-phenotype correlation

2016 ◽  
Vol 117 (3) ◽  
pp. 328-335 ◽  
Author(s):  
Nan Shen ◽  
Caroline Heintz ◽  
Christian Thiel ◽  
Jürgen G. Okun ◽  
Georg F. Hoffmann ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Phenylalanine Hydroxylase ◽  
Phenotype Correlation ◽  
Genotype Phenotype Correlation ◽  
Interallelic Complementation

scholarly journals Novel mutations of RPGR in Chinese families with X-linked retinitis pigmentosa

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhimeng Zhang ◽  
Hehua Dai ◽  
Lei Wang ◽  
Tianchang Tao ◽  
Jing Xu ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Mutation Screening ◽  
Phenotype Correlation ◽  
Novel Mutations ◽  
Pathological Myopia ◽  
Nonsense Mutations ◽  
Chinese Families ◽  
Coding Regions ◽  
Genotype Phenotype Correlation ◽  
Male Patients

Abstract Background RP (retinitis pigmentosa) is a group of hereditary retinal degenerative diseases. XLRP is a relatively severe subtype of RP. Thus, it is necessary to identify genes and mutations in patients who present with X-linked retinitis pigmentosa. Methods Genomic DNA was extracted from peripheral blood. The coding regions and intron-exon boundaries of the retinitis pigmentosa GTPase regulator (RPGR) and RP2 genes were amplified by PCR and then sequenced directly. Ophthalmic examinations were performed to identify affected individuals from two families and to characterize the phenotype of the disease. Results Mutation screening demonstrated two novel nonsense mutations (c.1541C > G; p.S514X and c.2833G > T; p.E945X) in the RPGR gene. The clinical manifestation of family 1 with mutations in exon 13 was mild. Genotype-phenotype correlation analysis suggested that patients with mutations close to the downstream region of ORF15 in family 2 manifested an early loss of cone function. Family 2 carried a nonsense mutation in ORF15 that appeared to have a semi-dominant pattern of inheritance. All male patients and two female carriers in family 2 manifested pathological myopia (PM), indicating that there may be a distinctive X-linked genotype-phenotype correlation between RP and PM. Conclusions We identified two novel mutations of the RPGR gene, which broadens the spectrum of RPGR mutations and the phenotypic spectrum of the disease in Chinese families.

Twenty-two novel mutations in the lysosomal ?-glucosidase gene (GAA) underscore the genotype-phenotype correlation in glycogen storage disease type II

2003 ◽  
Vol 23 (1) ◽  
pp. 47-56 ◽  
Author(s):  
Monique M.P. Hermans ◽  
Dik van Leenen ◽  
Marian A. Kroos ◽  
Clare E. Beesley ◽  
Ans T. Van der Ploeg ◽  
...  
Keyword(s):  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Type Ii ◽  
Phenotype Correlation ◽  
Novel Mutations ◽  
Genotype Phenotype Correlation

scholarly journals Structural characterization of the N-terminal autoregulatory sequence of phenylalanine hydroxylase

2002 ◽  
Vol 11 (8) ◽  
pp. 2041-2047 ◽  
Author(s):  
James Horne ◽  
Ian G. Jennings ◽  
Trazel Teh ◽  
Paul R. Gooley ◽  
Bostjan Kobe
Keyword(s):  
Structural Characterization ◽  
Phenylalanine Hydroxylase

Molecular characterization of myophosphorylase deficiency (McArdle disease) in 34 patients from Southern France: Identification of 10 new mutations. Absence of genotype–phenotype correlation

2007 ◽  
Vol 17 (3) ◽  
pp. 235-241 ◽  
Author(s):  
Robert Aquaron ◽  
Jean-louis Bergé-Lefranc ◽  
Jean-Francois Pellissier ◽  
Marie-France Montfort ◽  
Michèle Mayan ◽  
...  
Keyword(s):  
Molecular Characterization ◽  
Phenotype Correlation ◽  
Southern France ◽  
Mcardle Disease ◽  
Genotype Phenotype Correlation ◽  
New Mutations

Molecular Epidemiology of Phenylalanine Hydroxylase Deficiency in Southern Italy: a 96% Detection Rate with Ten Novel Mutations

2007 ◽  
Vol 71 (2) ◽  
pp. 185-193 ◽  
Author(s):  
A. Daniele ◽  
G. Cardillo ◽  
C. Pennino ◽  
M. T. Carbone ◽  
D. Scognamiglio ◽  
...  
Keyword(s):  
Molecular Epidemiology ◽  
Detection Rate ◽  
Southern Italy ◽  
Phenylalanine Hydroxylase ◽  
Novel Mutations ◽  
Hydroxylase Deficiency

scholarly journals Two novel mutations of the GTP cyclohydrolase 1 gene and genotype–phenotype correlation in Chinese Dopa-responsive dystonia patients

2012 ◽  
Vol 21 (7) ◽  
pp. 731-735 ◽  
Author(s):  
Lihua Yu ◽  
Huayong Zhou ◽  
Fayun Hu ◽  
Yanming Xu
Keyword(s):  
Gtp Cyclohydrolase ◽  
Phenotype Correlation ◽  
Novel Mutations ◽  
Genotype Phenotype Correlation

scholarly journals Mutation analysis of the ATP7B gene and genotype-phenotype correlation in Chinese patients with Wilson disease

2021 ◽  
Author(s):  
Mingming Li ◽  
Jing Ma ◽  
Wenlong Wang ◽  
Xu Yang ◽  
Kaizhong Luo
Keyword(s):  
Wilson Disease ◽  
Large Scale ◽  
Allelic Frequency ◽  
Chinese Patients ◽  
Missense Mutations ◽  
Onset Age ◽  
Phenotype Correlation ◽  
Novel Mutations ◽  
Nonsense Mutations ◽  
Genotype Phenotype Correlation

Abstract AIM To discover the novel ATP7B mutations in 103 southern Chinese patients with Wilson disease (WD), and to determine the spectrum and frequency of mutations in the ATP7B gene and genotype-phenotype correlation in a large-scale sample of Chinese WD patients. Methods One hundred three WD patients from 101 unrelated families in southern China were enrolled in this study. Genomic DNA was extracted from the peripheral blood. Direct sequencing of all 21 exons within ATP7B was performed. Subsequently, an extensive study of the overall spectrum and frequency of ATP7B mutations and genotype-phenotype correlation was performed in all Chinese patients eligible from the literature, combined with the current southern group.Results In 103 patients with WD, we identified 48 different mutations (42 missense mutations, 4 nonsense mutations and 2 frameshifts). Of these, 7 mutations had not been previously reported: 1510_1511insA, 2075T>C (Leu692Pro), 2233C>A (Leu745Met), 3209C>G (Pro1070Arg),3677C>T (Thr1226Ile), 3793G>T (Val1265Leu) and 3824T>C (Leu1275Ser). The 2333G>T (Arg778 Leu) at exon 8, was the most common mutation with an allelic frequency of 18.8%, followed by 2975C>T (Pro992Leu) at exon 13, with an allelic frequency of 13.4%. In the comprehensive study, 233 distinct mutations were identified, including 154 missense mutations, 23 nonsense mutations and 56 frameshifts. Eighty-five variants were identified as novel mutations. The 2333G>T (Arg778 Leu) and 2975C>T (Pro992Leu) were the most common mutations, with allelic frequencies of 28.6% and 13.0%, respectively. Exons 8, 12, 13, 16 and 18 were recognised as hot spot exons. Phenotype-genotype correlation analysis suggested that 2333G>T (Arg778 Leu) was significantly associated with lower levels of serum ceruloplasmin (P=0.034). 2975C>T (Pro992Leu) was correlated with earlier age of disease onset (P=0.002). Additionally, we found that the 3809A>G (Asn1270Ser) mutation significantly indicated younger onset age (P=0.012), and the 3884C>T (Ala1295Val) mutation at exon 18 was significantly associated with hepatic presentation (P=0.048). Moreover, the patients with mixed presentation displayed the initial WD features at an older onset age than the groups with either liver disease or neurological presentation (P=0.039, P=0.015, respectively). No significant difference was observed in the presence of KF rings among the three groups with different clinical manifestations. Conclusion In this study, we identified seven novel mutations in 103 WD patients from the southern part of China, which could enrich the previously established mutational spectrum of the ATP7B gene. Moreover, we tapped into a large-scale study of a Chinese WD cohort to characterise the overall phenotypic and genotypic spectra and assess the association between genotype and phenotype, which enhances the current knowledge about the population genetics of WD in China.

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