Key Laboratory of Reproductive Health of Liaoning Province

Shenyang, China

Key Laboratory of Reproductive Health of Liaoning Province

Shenyang, China
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Zhao N.,Key Laboratory of Reproductive Health of Liaoning Province | Jiang M.,Key Laboratory of Reproductive Health of Liaoning Province | Han W.,Key Laboratory of Reproductive Health of Liaoning Province | Bian C.,Affiliated Hospital of Liaoning Provincial Research Institute of Family Planning Institute | And 4 more authors.
European Journal of Medical Genetics | Year: 2011

Distal arthrogryposis (DA) is a group of rare, clinically and genetically heterogeneous disorders primarily characterized by congenital contractures of the limb joints. Recently, mutations in genes encoding the fast-twitch skeletal muscle contractile myofibers complex, including troponin I2 (TNNI2), troponin T3 (TNNT3), tropomyosine 2 (TPM2), and embryonic myosin heavy chain 3 (MYH3), and the slow-twitch skeletal muscle myosin binding protein C1 (MYBPC1) were confirmed to cause DA1, DA2A, and DA2B. DA2B, or Sheldon-Hall syndrome (SHS; MIM 601680), is intermediate to DA1 and DA2A, or Freeman-Sheldon syndrome (FSS; MIM193700), and shows prominent facial traits. This report describes a Chinese family with SHS over three generations in which all affected individuals showed vertical talus and one demonstrated preauricular tags on the face. Linkage analysis and PCR sequencing revealed a novel substitute mutation at a hot-spot site in TNNT3 (c.187C > T; p.R63C). This mutation was confirmed to cosegregate with the DA phenotype in affected individuals. SIFT and PolyPhen analyses suggest that the mutation is pathogenic. We report this mutation in TNNT3 and speculate that bilateral vertical talus, or severe clubfoot, might be a special characteristic for cases with the TNNT3 R63C mutation. © 2011 Elsevier Masson SAS.


Wang Y.W.,Key Laboratory of Reproductive Health of Liaoning Province | Han W.T.,Key Laboratory of Reproductive Health of Liaoning Province | Jiang M.,Key Laboratory of Reproductive Health of Liaoning Province | Lu C.X.,Peking Union Medical College | And 3 more authors.
Genetics and Molecular Research | Year: 2012

Charcot-Marie-Tooth (CMT) is a group of clinically and genetically heterogeneous inherited neuromuscular disorders. At present, more than 30 loci have been reported to be associated with CMT disease; point mutations in the mitofusin 2 (MFN2) gene is one of the most common causes. We studied a Chinese family with CMT disease in which the phenotype of affected individuals varied, and the weakness condition of the distal legs in males, except the proband, was less severe than in females in this family. Linkage analysis and PCR sequencing revealed a missense mutation (NM_014874.3:c.1066 A>G) in the MFN2 gene, resulting in an animo acid substitution of threonine to alanine in condon 356 (Thr356Ala). This is a novel phenotype and mutation for CMT family. © FUNPEC-RP.


Li X.,Key Laboratory of Reproductive Health of Liaoning Province | Jiang M.,Key Laboratory of Reproductive Health of Liaoning Province | Han W.,Key Laboratory of Reproductive Health of Liaoning Province | Zhao N.,Key Laboratory of Reproductive Health of Liaoning Province | And 4 more authors.
Gene | Year: 2013

Distal arthrogryposes (DAs), a clinically and genetically heterogeneous group of disorders characterized by congenital contractures with predominant involvement of the hands and feet, can be classified into at least 12 different forms. These autosomal dominant disorders are of variable expressivity and reduced penetrance. Mutations in sarcomeric protein genes, including troponin I2 (TNNI2), troponin T3 (TNNT3), tropomyosin 2 (TPM2), embryonic myosin heavy chain 3 (MYH3), and myosin binding protein C1 (MYBPC1), have been identified in distal arthrogryposis type 1 (DA1, MIM 108120), type 2B (DA2B, MIM 601680) and type 2A (DA2A)/Freeman-Sheldon syndrome (FSS, MIM 193700). However, mutations causing FSS have only been reported in MYH3. Herein we describe a Chinese DA family whose members meet classical strict criteria for FSS, as well as one member of the family who has isolated facial features consistent with FSS. No disease-causing mutation was found in MYH3. Segregation of microsatellite markers flanking the TNNI2 and TNNT3 genes at 11p15.5 was compatible with linkage. Subsequent sequencing of TNNI2 revealed a novel mutation, c.A493T (p.I165F), located in the C-terminal region, which is critical for proper protein function. This mutation was found to cosegregate with the FSS phenotype in this family, and assessment using SIFT and PolyPhen-2 predicted a damaging effect. To the best of our knowledge, we report the first TNNI2 mutation in classical FSS and describe an atypical adult FSS case with only facial contractures resulting from somatic mosaicism. We infer that DA1, DA2B and FSS represent a phenotypic continuum of the same disorder and provide further genetic evidence for this hypothesis. © 2013 Elsevier B.V.


Sui Y.,Key Laboratory of Reproductive Health of Liaoning Province | Sui Y.,Research Institute of Family Planning of Liaoning Province | Han W.,Key Laboratory of Reproductive Health of Liaoning Province | Han W.,Research Institute of Family Planning of Liaoning Province | And 4 more authors.
European Journal of Obstetrics Gynecology and Reproductive Biology | Year: 2011

Objectives: An accumulation of evidence suggests that gene-based self-susceptibility may contribute to the development of cancer. Some studies have found that particular polymorphisms of the glutathione S-transferase M1 and T1 genes are associated with increased risk of cervical lesions, but other studies have had contrary results. The present meta-analysis evaluated the association of glutathione S-transferase M1 and T1 null polymorphisms with the development of cervical lesions. In addition, stratified analyses were performed in an attempt to identify any race-specific effects. Study design: Twenty-one related studies were included in the meta-analysis, comprising glutathione S-transferase M1 data from 1423 patients with cervical lesions and 2415 healthy matched controls, and glutathione S-transferase T1 data from 2081 patients with cervical lesions and 2287 healthy matched controls. The fixed-effect model (Mantel-Haenszel method) and the random-effect (DerSimonian and Laird) model were used to examine the difference in frequency of glutathione S-transferase M1 and T1 null polymorphisms between pre- and invasive cervical lesions. Subgroup analyses were also conducted to evaluate any race-specific effect on the frequencies of glutathione S-transferase polymorphisms in cervical lesions. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Heterogeneity was assessed using the heterogeneity metric (I 2) and Chi-squared test. Results: The glutathione S-transferase M1 null polymorphism was associated with increased risk of low-grade intra-epithelial lesions (OR 1.37, 95% CI 1.05-1.77), but no increased risk of high-grade intra-epithelial lesions (OR 1.29, 95% CI 0.87-1.8) or invasive cervical cancer (OR 1.20, 95% CI 0.99-1.46). The association seemed to be confined to Southeast Asians (OR 1.97, 95% CI 1.44-2.71). No significant associations were found for the glutathione S-transferase T1 null polymorphism for any of the populations. Conclusions: The glutathione S-transferase M1 null polymorphism significantly increases susceptibility to early-stage cervical lesions in Southeast Asians. However, the glutathione S-transferase T1 null polymorphism does not appear to be a risk factor for cervical lesions in any population. Copyright © 2011 Published by Elsevier Ireland Ltd. All rights reserved.


Li X.,Key Laboratory of Reproductive Health of Liaoning Province | Zhong B.,Nanjing First Hospital | Han W.,Key Laboratory of Reproductive Health of Liaoning Province | Zhao N.,Key Laboratory of Reproductive Health of Liaoning Province | And 7 more authors.
PLoS ONE | Year: 2015

Distal arthrogryposes (DAs) are a group of disorders that mainly involve the distal parts of the limbs and at least ten different DAs have been described to date. DAs are mostly described as autosomal dominant disorders with variable expressivity and incomplete penetrance, but recently autosomal recessive pattern was reported in distal arthrogryposis type 5D. Mutations in the contractile genes are found in about 50% of all DA patients. Of these genes, mutations in the gene encoding myosin binding protein C slow MYBPC1 were recently identified in two families with distal arthrogryposis type 1B. Here, we described two large Chinese families with autosomal dominant distal arthrogryposis type 2(DA2) with incomplete penetrance and variable expressivity. Some unique overextension contractures of the lower limbs and some distinctive facial features were present in our DA2 pedigrees. We performed follow-up DNA sequencing after linkage mapping and first identified two novel MYBPC1 mutations (c.1075G>A [p.E359K] and c.956C>T [p.P319L]) responsible for these Chinese DA2 families of which one introduced by germline mosacism. Each mutation was found to cosegregate with the DA2 phenotype in each family but not in population controls. Both substitutions occur within C2 immunoglobulin domain, which together with C1 and the M motif constitute the binding site for the S2 subfragment of myosin. Our results expand the phenotypic spectrum of MYBPC1-related arthrogryposis multiplex congenita (AMC). We also proposed the possible molecular mechanisms that may underlie the pathogenesis of DA2 myopathy associated with these two substitutions in MYBPC1. © 2015 Li et al.


PubMed | Nanjing First Hospital and Key Laboratory of Reproductive Health of Liaoning Province
Type: Journal Article | Journal: PloS one | Year: 2015

Distal arthrogryposes (DAs) are a group of disorders that mainly involve the distal parts of the limbs and at least ten different DAs have been described to date. DAs are mostly described as autosomal dominant disorders with variable expressivity and incomplete penetrance, but recently autosomal recessive pattern was reported in distal arthrogryposis type 5D. Mutations in the contractile genes are found in about 50% of all DA patients. Of these genes, mutations in the gene encoding myosin binding protein C slow MYBPC1 were recently identified in two families with distal arthrogryposis type 1B. Here, we described two large Chinese families with autosomal dominant distal arthrogryposis type 2(DA2) with incomplete penetrance and variable expressivity. Some unique overextension contractures of the lower limbs and some distinctive facial features were present in our DA2 pedigrees. We performed follow-up DNA sequencing after linkage mapping and first identified two novel MYBPC1 mutations (c.1075G>A [p.E359K] and c.956C>T [p.P319L]) responsible for these Chinese DA2 families of which one introduced by germline mosacism. Each mutation was found to cosegregate with the DA2 phenotype in each family but not in population controls. Both substitutions occur within C2 immunoglobulin domain, which together with C1 and the M motif constitute the binding site for the S2 subfragment of myosin. Our results expand the phenotypic spectrum of MYBPC1-related arthrogryposis multiplex congenita (AMC). We also proposed the possible molecular mechanisms that may underlie the pathogenesis of DA2 myopathy associated with these two substitutions in MYBPC1.


Li X.,Key Laboratory of Reproductive Health of Liaoning Province | Jiang M.,Key Laboratory of Reproductive Health of Liaoning Province | Han W.,Key Laboratory of Reproductive Health of Liaoning Province
European Journal of Medical Genetics | Year: 2013

Letter to the editor on a recent publication of Hofmann, K., etal. (2011). "7Mb de novo deletion within 8q21 in a patient with distal arthrogryposis type 2B (DA2B)." in the European Journal of Medical Genetics. The author may suggest a further heterogeneous locus contained in 8q21 for Freeman-Sheldon syndrome. © 2013 Elsevier Masson SAS.


PubMed | Key Laboratory of Reproductive Health of Liaoning Province
Type: Journal Article | Journal: European journal of medical genetics | Year: 2011

Distal arthrogryposis (DA) is a group of rare, clinically and genetically heterogeneous disorders primarily characterized by congenital contractures of the limb joints. Recently, mutations in genes encoding the fast-twitch skeletal muscle contractile myofibers complex, including troponin I2 (TNNI2), troponin T3 (TNNT3), tropomyosine 2 (TPM2), and embryonic myosin heavy chain 3 (MYH3), and the slow-twitch skeletal muscle myosin binding protein C1 (MYBPC1) were confirmed to cause DA1, DA2A, and DA2B. DA2B, or Sheldon-Hall syndrome (SHS; MIM 601680), is intermediate to DA1 and DA2A, or Freeman-Sheldon syndrome (FSS; MIM193700), and shows prominent facial traits. This report describes a Chinese family with SHS over three generations in which all affected individuals showed vertical talus and one demonstrated preauricular tags on the face. Linkage analysis and PCR sequencing revealed a novel substitute mutation at a hot-spot site in TNNT3 (c.187C > T; p.R63C). This mutation was confirmed to cosegregate with the DA phenotype in affected individuals. SIFT and PolyPhen analyses suggest that the mutation is pathogenic. We report this mutation in TNNT3 and speculate that bilateral vertical talus, or severe clubfoot, might be a special characteristic for cases with the TNNT3 R63C mutation.


PubMed | Key Laboratory of Reproductive Health of Liaoning Province
Type: Journal Article | Journal: European journal of obstetrics, gynecology, and reproductive biology | Year: 2011

An accumulation of evidence suggests that gene-based self-susceptibility may contribute to the development of cancer. Some studies have found that particular polymorphisms of the glutathione S-transferase M1 and T1 genes are associated with increased risk of cervical lesions, but other studies have had contrary results. The present meta-analysis evaluated the association of glutathione S-transferase M1 and T1 null polymorphisms with the development of cervical lesions. In addition, stratified analyses were performed in an attempt to identify any race-specific effects.Twenty-one related studies were included in the meta-analysis, comprising glutathione S-transferase M1 data from 1423 patients with cervical lesions and 2415 healthy matched controls, and glutathione S-transferase T1 data from 2081 patients with cervical lesions and 2287 healthy matched controls. The fixed-effect model (Mantel-Haenszel method) and the random-effect (DerSimonian and Laird) model were used to examine the difference in frequency of glutathione S-transferase M1 and T1 null polymorphisms between pre- and invasive cervical lesions. Subgroup analyses were also conducted to evaluate any race-specific effect on the frequencies of glutathione S-transferase polymorphisms in cervical lesions. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Heterogeneity was assessed using the heterogeneity metric (I) and Chi-squared test.The glutathione S-transferase M1 null polymorphism was associated with increased risk of low-grade intra-epithelial lesions (OR 1.37, 95% CI 1.05-1.77), but no increased risk of high-grade intra-epithelial lesions (OR 1.29, 95% CI 0.87-1.8) or invasive cervical cancer (OR 1.20, 95% CI 0.99-1.46). The association seemed to be confined to Southeast Asians (OR 1.97, 95% CI 1.44-2.71). No significant associations were found for the glutathione S-transferase T1 null polymorphism for any of the populations.The glutathione S-transferase M1 null polymorphism significantly increases susceptibility to early-stage cervical lesions in Southeast Asians. However, the glutathione S-transferase T1 null polymorphism does not appear to be a risk factor for cervical lesions in any population.


PubMed | Key Laboratory of Reproductive Health of Liaoning Province
Type: Journal Article | Journal: Genetics and molecular research : GMR | Year: 2012

Charcot-Marie-Tooth (CMT) is a group of clinically and genetically heterogeneous inherited neuromuscular disorders. At present, more than 30 loci have been reported to be associated with CMT disease; point mutations in the mitofusin 2 (MFN2) gene is one of the most common causes. We studied a Chinese family with CMT disease in which the phenotype of affected individuals varied, and the weakness condition of the distal legs in males, except the proband, was less severe than in females in this family. Linkage analysis and PCR sequencing revealed a missense mutation (NM_014874.3:c.1066 A>G) in the MFN2 gene, resulting in an animo acid substitution of threonine to alanine in condon 356 (Thr356Ala). This is a novel phenotype and mutation for CMT family.

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