scholarly journals Clinical Characteristics And Identification of Novel TGF-β1 Mutation In Three Unrelated Chinese Families With Progressive Diaphyseal Dysplasia

2021 ◽  
Author(s):  
Xiao-Hui Tao ◽  
Xing-Guang Yang ◽  
Zi-Yuan Wang ◽  
Yang Xu ◽  
Zhen-Lin Zhang ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Clinical Characteristics ◽  
Novel Mutation ◽  
The Novel ◽  
Chinese Families ◽  
Progressive Diaphyseal Dysplasia ◽  
Exon 4 ◽  
Diaphyseal Dysplasia ◽  
Tgf Β1

Abstract BackgroundTo investigate the clinical characteristics and molecular diagnosis of progressive diaphyseal dysplasia (PDD) in three unrelated Chinese families. MethodsThe present study recruited six patients aged 14 to 45 from three unrelated families with PDD, including five females and one male. Clinical manifestations, biochemical tests, radiographic examinations were analyzed and the TGF-β1 gene mutation was further identified by Sanger sequencing. In addition, data of treatment and follow-up were also collected.ResultsThe onset age of the patients ranged from 1 to 6 years. All the affected patients had family histories and were consisted with autosomal dominant inheritance pattern. All of them exhibited gait disturbance, fatigue, progressive bone pain, as well as muscle atrophy and weakness in limbs. Notably, there was one 15-year-old girl who experienced heart valve defects and tachycardia at birth. Laboratory examinations revealed the inflammatory markers were in high level, besides the extremely increased bone metabolism indicators. The thickened diaphysis of long bones and the narrowed medullary cavity were observed by radiography. Furthermore, radionuclide bone scan detected abnormal symmetrical radioactive concentration in the affected regions of bone. Sanger sequencing identified a missense heterozygous mutation in exon 4 of TGF-β1 gene, resulting in R218C, which confirmed PDD eventually. More important, a novel mutation c.669C>G in exon 4 of TGF-β1 gene harboring C223W were detected in family 3. Subsequent bioinformatics software predicted that the novel mutation was pathogenic. Our study also showed that zoledronic acid was not effective in the control of bone turnover markers and the relief of bone pain in patients with PDD.ConclusionIn addition to the typical PDD manifestations, the new phenotypic characteristics such as tachycardia and heart valve defect were firstly reported in one female patient carried the novel mutation p.Cys223Trp in TGF-β1 gene. In addition, our study indicated that the increased bone metabolism indicators and inflammatory markers may possess auxiliary diagnosis for PDD. More importantly, zoledronic acid was used to treat PDD patients in this study. After one-year follow-up, it was proved that the drug effect was not satisfactory, and new drugs need to be developed to treat the disease.

Progressive Diaphyseal Dysplasia: Genetics and Clinical and Radiologic Manifestations

PEDIATRICS ◽  
1984 ◽  
Vol 74 (3) ◽  
pp. 399-405
Author(s):  
Yehezkel Naveh ◽  
Joseph K. Kaftori ◽  
Uri Alon ◽  
Jacob Ben-David ◽  
Moshe Berant
Keyword(s):  
Autosomal Dominant ◽  
Autosomal Dominant Disorder ◽  
Generation Family ◽  
Progressive Diaphyseal Dysplasia ◽  
Radiographic Screening ◽  
Osteosclerotic Dysplasia ◽  
Structural Deformity ◽  
Diaphyseal Dysplasia ◽  
Engelmann Disease

Progressive diaphyseal dysplasia was found in a three-generation family including 13 affected individuals, the largest family reported to date. Our study confirms that progressive diaphyseal dysplasia, also known as Engelmann's or Camurati-Engelmann disease, is an autosomal dominant disorder with variable osseous and muscular manifestations. Disease distribution among patients, within a given patient, or even in individual bones is unpredictable. The femur is the most commonly and severely affected bone and hence most useful for radiographic screening of possible patients. Radiographs provide a meaningful assessment of disease activity and extent. The severity of symptoms is generally proportionate to severity of involvement shown by roentgenography. Exophthalmos due to osteosclerotic dysplasia of the skull occurred in more than half of the patients with progressive diaphyseal dysplasia. Twelve-year follow-up of this family, with affected individuals ranging in age from 6 months to 12 years, indicates that progressive diaphyseal dysplasia may progress or become quiescent and be remarkably inactive despite advanced osteosclerosis and structural deformity.

scholarly journals Two novel mutations in the ALPL gene of unrelated Chinese children with Hypophosphatasia: case reports and literature review

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaojian Mao ◽  
Sichi Liu ◽  
Yunting Lin ◽  
Zhen Chen ◽  
Yongxian Shao ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Novel Mutation ◽  
Case Reports ◽  
Chinese Children ◽  
Deciduous Teeth ◽  
Missense Mutations ◽  
The Novel ◽  
Genetic Characteristics ◽  
Chinese Families ◽  
Alp Activity

Abstract Objective Hypophosphatasia (HPP) is an inherited disorder of defective skeletal mineralization caused by mutations in the ALPL gene that encodes the Tissue Non-specific Alkaline Phosphatase (TNSALP). It is subdivided into six forms depending on the age of onset: perinatal lethal, prenatal benign, infantile, childhood, adult, and odonto HPP. Among these, infantile HPP is characterized by early onset and high frequency of lethal outcome. Few studies have reported the phenotype and genetic characteristics of HPP in Chinese children. Case presentation Three forms of HPP were identified in four unrelated patients from four different Chinese families, including one lethal infantile (patient 1), two childhood (patient 2 and 3) and one odonto HPP (patient 4). Six variants in the ALPL gene were identified, including five missense mutations and one frameshift mutation. Of which, none were reported previously in the Chinese population, and two were novel (c.359G > C: p.G120A and c.1017dupG: p.H340AfsX3). Patient 1 carrying a novel homozygous (c.359G > C) mutation showed respiratory distress and pneumonia at first day of his life. He presented nearly negligible level of serum ALP activity, overall skeletal hypominaralization and died at 3 months old. Patient 2, 3 and 4 were compound heterozygotes with decreased serum ALP activity. Patient 2 and 3 presented premature loss of deciduous teeth, muscle weakness and bone pain, whereas patient 4 had early loss of deciduous teeth only. All four pedigrees exhibited autosomal recessive pattern of inheritance. Conclusions In this study, six mutations in the ALPL gene were found in four Chinese HPP patients, two of which were novel: c.359G > C in exon 5 and c.1017dupG in exon 10. Our results strongly indicated that the novel mutation c.359G > C might be disease-causing and associated with severe infantile form of HPP.

scholarly journals Clinical and genetic analysis of two Chinese families with vitamin D-dependent rickets type IA and follow-up

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Yunfei Li ◽  
Xin Yuan ◽  
Ruimin Chen ◽  
Xiangquan Lin ◽  
Huakun Shangguan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Serum Calcium ◽  
Clinical Characteristics ◽  
Serum Alkaline Phosphatase ◽  
Laboratory Data ◽  
Clinical Manifestations ◽  
Individual Therapy ◽  
Chinese Families ◽  
Type Ia

Abstract Objective Vitamin D-dependent rickets type IA (VDDR-IA) is a rare autosomal recessive disorder characterized by the early onset of severe rickets. The objectives of this study were twofold: (1) to analyze the clinical characteristics and therapy of two patients with VDDR-IA from two separate Chinese families, and (2) investigate the CYP27B1 gene mutations in two large pedigrees. Methods Medical history, clinical manifestations, physical examination, radiological findings and laboratory data were analyzed from two patients with VDDR-IA. Serum 1, 25-dihydroxyvitamin D [1, 25-(OH)2D3] of the two patients and their respective families were measured by ELISA and blood samples from both families was obtained for CYP27B1 gene sequence. Results Two patients had typical manifestations and radiological evidence of rickets. Laboratory data showed hypocalcaemia and hypophosphataemia, along with high levels of serum alkaline phosphatase, parathyroid hormone and 25-hydroxyvitamin D3. However, serum 1,25-(OH)2D3 level were low in the patients but normal in their family members. Genetic sequence identified two patients were homozygous for a duplication mutation in exon 8 of CYP27B1 gene (c.1319_1325dupCCCACCC, p.Phe443Profs * 24). After treating with calcitriol and calcium, there was biochemical improvement with normalization of serum calcium and phosphorus, and radiographic evidence of compensatory skeletal mineralization. One patient developed nephrocalcinosis during follow-up. Conclusions This study identified a recurrent seven-nucleotide insertion of CYP27B1 in two large pedigrees, and compared the clinical characteristics and individual therapy of two affected patients. Additionally, our experience further supports the notion that nephrocalcinosis can occur even on standard doses of calcitriol and oral calcium, and normal level of serum calcium, phosphorus, PTH and 25-(OH)D3.

scholarly journals Clinical characteristics of 134 convalescent patients with COVID-19 in Guizhou, China

2020 ◽  
Author(s):  
Siqin Zhang ◽  
Lin Liu ◽  
Bin Yang ◽  
Rou Li ◽  
Jianhua Luo ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Laboratory Data ◽  
Ground Glass Opacity ◽  
Ground Glass ◽  
The Novel ◽  
Positive Rate ◽  
Discharged Patients ◽  
Treatment Plans ◽  
Normal Chest

Abstract Background: Previous studies have focused on the clinical characteristics of hospitalized patients with the novel 2019 coronavirus disease (COVID-19). Limited data are available for convalescent patients. This study aimed to evaluate the clinical characteristics of discharged COVID-19 patients.Methods: In this retrospective study, we extracted data for 134 convalescent patients with COVID-19 in Guizhou Provincial Staff Hospital from February 15 to March 31, 2020. Cases were analyzed on the basis of demographic, clinical, and laboratory data as well as radiological features. Results: Of 134 convalescent patients with COVID-19, 19 (14.2%) were severe cases, while 115 (85.8%) were non-severe cases. The median patient age was 33 years (IQR, 21.8 to 46.3), and the cohort included 69 men and 65 women. Compared with non-severe cases, severe patients were older and had more chronic comorbidities, especially hypertension, diabetes, and thyroid disease (P<0.05). Leukopenia was present in 32.1% of the convalescent patients and lymphocytopenia was present in 6.7%, both of which were more common in severe patients. 48 (35.8%) of discharged patients had elevated levels of alanine aminotransferase, which was more common in adults than in children (40.2% vs 13.6%, P=0.018). A normal chest CT was found in 61 (45.5%) patients during rehabilitation. Severe patients had more ground-glass opacity, bilateral patchy shadowing, and fibrosis. No significant differences were observed in the positive rate of IgG and/or IgM antibodies between severe and non-severe patients.Conclusion: Leukopenia, lymphopenia, ground-glass opacity, and fibrosis are common in discharged severe COVID-19 patients, and liver injury is common in discharged adult patients. We suggest physicians develop follow-up treatment plans based on the different clinical characteristics of convalescent patients.

scholarly journals Two Novel Mutations in the ALPL gene of Unrelated Chinese Children with Hypophosphatasia: Case Reports and Literature Review

2019 ◽  
Author(s):  
Xiaojian Mao ◽  
Sichi Liu ◽  
Yunting Lin ◽  
Zhen Chen ◽  
Yongxian Shao ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Novel Mutation ◽  
Case Reports ◽  
Chinese Children ◽  
Deciduous Teeth ◽  
Missense Mutations ◽  
The Novel ◽  
Genetic Characteristics ◽  
Chinese Families ◽  
Alp Activity

Abstract Objective: Hypophosphatasia (HPP) is an inherited disorder of defective skeletal mineralization caused by mutations in the ALPL gene that encodes the Tissue Non-specific Alkaline Phosphatase (TNSALP). It is subdivided into six forms depending on the age of onset: perinatal lethal, prenatal benign, infantile, childhood, adult, and odonto HPP. Among these, infantile HPP is characterized by early onset and high frequency of lethal outcome. Few studies have reported the phenotype and genetic characteristics of HPP in Chinese children. Case presentation: Three forms of HPP were identified in four unrelated patients from four different Chinese families, including one lethal infantile (patient 1), two childhood (patient 2 and 3) and one odonto HPP (patient 4). Six variants in the ALPL gene were identified, including five missense mutations and one frameshift mutation. Of which, none were reported previously in the Chinese population, and two were novel (c.359G>C: p.G120A and c.1017dupG: p.H340AfsX3). Patient 1 carrying a novel homozygous (c.359G>C) mutation showed respiratory distress and pneumonia at first day of his life. He presented nearly negligible level of serum ALP activity, overall skeletal hypominaralization and died at 3 months old. Patient 2, 3 and 4 were compound heterozygotes with decreased serum ALP activity. Patient 2 and 3 presented premature loss of deciduous teeth, muscle weakness and bone pain, whereas patient 4 had early loss of deciduous teeth only. All four pedigrees exhibited autosomal recessive pattern of inheritance. Conclusions: In this study, six mutations in the ALPL gene were found in four Chinese HPP patients. Two of which were novel: c.359G>C in exon 5 and c.1017dupG in exon 10. Our results strongly indicated that the novel mutation c.359G>C might be disease-causing and associated with severe infantile form of HPP.

scholarly journals Two Novel Mutations in the ALPL gene of Unrelated Chinese Children with Hypophosphatasia: Case Reports and Literature Review

2019 ◽  
Author(s):  
Xiaojian Mao ◽  
Sichi Liu ◽  
Yunting Lin ◽  
Zhen Chen ◽  
Yongxian Shao ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Novel Mutation ◽  
Case Reports ◽  
Chinese Children ◽  
Deciduous Teeth ◽  
Missense Mutations ◽  
The Novel ◽  
Genetic Characteristics ◽  
Chinese Families ◽  
Alp Activity

Abstract Objective: Hypophosphatasia (HPP) is an inherited disorder of defective skeletal mineralization caused by mutations in the ALPL gene that encodes the Tissue Non-specific Alkaline Phosphatase (TNSALP). It is subdivided into six forms depending on the age of onset: perinatal lethal, prenatal benign, infantile, childhood, adult, and odonto HPP. Among these, infantile HPP is characterized by early onset and high frequency of lethal outcome. Few studies have reported the phenotype and genetic characteristics of HPP in Chinese children. Case presentation: Three forms of HPP were identified in four unrelated patients from four different Chinese families, including one lethal infantile (patient 1), two childhood (patient 2 and 3) and one odonto HPP (patient 4). Six variants in the ALPL gene were identified, including five missense mutations and one frameshift mutation. Of which, none were reported previously in the Chinese population, and two were novel (c.359G>C: p.G120A and c.1017dupG: p.H340AfsX3). Patient 1 carrying a novel homozygous (c.359G>C) mutation showed respiratory distress and pneumonia at first day of his life. He presented nearly negligible level of serum ALP activity, overall skeletal hypominaralization and died at 3 months old. Patient 2, 3 and 4 were compound heterozygotes with decreased serum ALP activity. Patient 2 and 3 presented premature loss of deciduous teeth, muscle weakness and bone pain, whereas patient 4 had early loss of deciduous teeth only. All four pedigrees exhibited autosomal recessive pattern of inheritance. Conclusions: In this study, six mutations in the ALPL gene were found in four Chinese HPP patients. Two of which were novel: c.359G>C in exon 5 and c.1017dupG in exon 10. Our results show that the novel mutation c.359G>C is strongly indicated to be disease-causing and associated with severe infantile form of HPP.

scholarly journals A Case Report and Literature Review of a Novel Mutation in the MAGED2 Gene of a Patient With Severe Transient Polyhydramnios

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaoxia Wu ◽  
Le Huang ◽  
Caiqun Luo ◽  
Yang Liu ◽  
Jianmin Niu
Keyword(s):  
Clinical Characteristics ◽  
Frameshift Mutation ◽  
Novel Mutation ◽  
Bartter’S Syndrome ◽  
Bartter's Syndrome ◽  
Case Presentation ◽  
New Novel ◽  
Novel Variant ◽  
Antenatal Bartter’S Syndrome

Background: Polyhydramnios occurs frequently during pregnancy. Mutations in the MAGED2 gene can cause X-linked acute early-onset polyhydramnios with a severe but transient form of antenatal Bartter's syndrome.Case Presentation: Here, we report a new novel frameshift mutation c.733_734delCT (p. Leu245GlufsTer4) in the MAGED2 gene (NM_177433.1) that caused prenatal polyhydramnios, but did not cause polyuria after birth. Follow-up was conducted for 2 months, and the baby's growth and development were normal, without polyuria and renal impairment. In addition, we identified all individuals with MAGED2 mutations reported in the literature before March 2021.Conclusion: We report a new case with a novel variant of the MAGED2 gene that caused severe hydramnios but with a good result and summary clinical characteristics in a newborn with antenatal Bartter's syndrome caused by an MAGED2 mutation. Good prenatal diagnosis and genetic consultation can improve pregnancy monitoring and newborn management.

scholarly journals Two Novel Mutations in the ALPL gene of Unrelated Chinese Children with Hypophosphatasia: Case Reports and Literature Review

2019 ◽  
Author(s):  
Xiaojian Mao ◽  
Sichi Liu ◽  
Yunting Lin ◽  
Zhen Chen ◽  
Yongxian Shao ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Novel Mutation ◽  
Case Reports ◽  
Chinese Children ◽  
Deciduous Teeth ◽  
Missense Mutations ◽  
The Novel ◽  
Genetic Characteristics ◽  
Chinese Families ◽  
Alp Activity

Abstract Objective: Hypophosphatasia (HPP) is an inherited disorder of defective skeletal mineralization caused by mutations in the ALPL gene that encodes the Tissue Non-specific Alkaline Phosphatase (TNSALP). It is subdivided into six forms depending on the age of onset: perinatal lethal, prenatal benign, infantile, childhood, adult, and odonto HPP. Among these, infantile HPP is characterized by early onset and high frequency of lethal outcome. Few studies have reported the phenotype and genetic characteristics of HPP in Chinese children. Case presentation: Three forms of HPP were identified in four unrelated patients from four different Chinese families, including one lethal infantile (patient 1), two childhood (patient 2 and 3) and one odonto HPP (patient 4). Six variants in the ALPL gene were identified, including five missense mutations and one frameshift mutation. Of which, none were reported previously in the Chinese population, and two were novel (c.359G>C: p.G120A and c.1017dupG: p.H340AfsX3). Patient 1 carrying a novel homozygous (c.359G>C) mutation showed respiratory distress and pneumonia at first day of his life. He presented nearly negligible level of serum ALP activity, overall skeletal hypominaralization and died at 3 months old. Patient 2, 3 and 4 were compound heterozygotes with decreased serum ALP activity. Patient 2 and 3 presented premature loss of deciduous teeth, muscle weakness and bone pain, whereas patient 4 had early loss of deciduous teeth only. All four pedigrees exhibited autosomal recessive pattern of inheritance. Conclusions: In this study, six mutations in the ALPL gene were found in four Chinese HPP patients. Two of which were novel: c.359G>C in exon 5 and c.1017dupG in exon 10. Our results strongly indicated that the novel mutation c.359G>C might be disease-causing and associated with severe infantile form of HPP.

scholarly journals Clinical characteristics of 134 convalescent patients with COVID-19 in Guizhou, China

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Siqin Zhang ◽  
Lin Liu ◽  
Bin Yang ◽  
Rou Li ◽  
Jianhua Luo ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Laboratory Data ◽  
Ground Glass Opacity ◽  
Ground Glass ◽  
The Novel ◽  
Positive Rate ◽  
Discharged Patients ◽  
Treatment Plans ◽  
Normal Chest

Abstract Background Previous studies have focused on the clinical characteristics of hospitalized patients with the novel 2019 coronavirus disease (COVID-19). Limited data are available for convalescent patients. This study aimed to evaluate the clinical characteristics of discharged COVID-19 patients. Methods In this retrospective study, we extracted data for 134 convalescent patients with COVID-19 in Guizhou Provincial Staff Hospital from February 15 to March 31, 2020. Cases were analyzed on the basis of demographic, clinical, and laboratory data as well as radiological features. Results Of 134 convalescent patients with COVID-19, 19 (14.2%) were severe cases, while 115 (85.8%) were non-severe cases. The median patient age was 33 years (IQR, 21.8 to 46.3), and the cohort included 69 men and 65 women. Compared with non-severe cases, severe patients were older and had more chronic comorbidities, especially hypertension, diabetes, and thyroid disease (P < 0.05). Leukopenia was present in 32.1% of the convalescent patients and lymphocytopenia was present in 6.7%, both of which were more common in severe patients. 48 (35.8%) of discharged patients had elevated levels of alanine aminotransferase, which was more common in adults than in children (40.2% vs 13.6%, P = 0.018). A normal chest CT was found in 61 (45.5%) patients during rehabilitation. Severe patients had more ground-glass opacity, bilateral patchy shadowing, and fibrosis. No significant differences were observed in the positive rate of IgG and/or IgM antibodies between severe and non-severe patients. Conclusion Leukopenia, lymphopenia, ground-glass opacity, and fibrosis are common in discharged severe COVID-19 patients, and liver injury is common in discharged adult patients. We suggest physicians develop follow-up treatment plans based on the different clinical characteristics of convalescent patients.

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