Unmasking a recessive allele by a deletion: Early prenatal diagnosis of Bardet‐Biedl syndrome in a Chinese family

2021 ◽  
Author(s):  
Xiang‐Yi Jing ◽  
Fan Jiang ◽  
Dong‐Zhi Li
Keyword(s):  
Prenatal Diagnosis ◽  
Recessive Allele ◽  
Chinese Family ◽  
Bardet Biedl Syndrome

The First Reported Case of Prenatal Diagnosis for Pyruvate Kinase Deficiency in a Chinese Family

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5276-5276
Author(s):  
Jason CC So ◽  
Mary Tang ◽  
Rever Li ◽  
Shau Yin Ha ◽  
Serge Pissard ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Prenatal Diagnosis ◽  
Ethnic Groups ◽  
Pyruvate Kinase ◽  
Hemolytic Anemia ◽  
Pediatric Patients ◽  
Conflicts Of Interest ◽  
Chinese Family ◽  
First Case

Abstract Abstract 5276 Pyruvate kinase (PK) deficiency of red cells (EC: 2.7.1.40) is the commonest inherited enzyme deficiency in the glycolytic pathway, leading to chronic non-spherocytic hemolytic anemia (CNSHA). There are over 220 characterized mutations deposited in a public database (PKLR Mutation Database http://www.pklrmutationdatabase.com). Heterozygous carriers are asymptomatic but homozygotes or compound heterozygotes can have significant anemia leading to transfusion dependency, neonatal death and hydrops fetalis. All ethnic groups are affected but data on Chinese are very scanty. We describe the first case of prenatal diagnosis for PK deficiency in Chinese and emphasize that this disease is an important differential diagnosis in pediatric patients with hemolytic anemia. A Han Chinese presented with hepatosplenomegaly, severe anemia and unconjugated hyperbilirubinemia at birth, necessitating exchange transfusion on day 1 and prolonged phototherapy till day 10 of life. Glucose-6-phosphate dehydrogenase level was normal. His parents were unrelated and asymptomatic. Family history was unremarkable. He developed severe CNSHA on follow up, requiring monthly red cell transfusion to relieve symptoms and to maintain satisfactory growth. Iron chelation therapy was started at 2 years of age and splenectomy was performed at 4 years to reduce transfusion requirement. The baseline PK enzyme level was not known but both parents had a mildly reduced PK level. Genetic analysis of PKLR gene was performed. All 11 exons and promoter were screened using polymerase chain reaction (PCR)-denaturing high performance liquid chromatography followed by PCR-sequencing. The father was found to carry a mutation in exon 8: PKLR: c.1073 G>A (p.Gly358Glu) while the sequencing result was normal in the mother. Quantitative multiplex PCR of short fluorescent fragments detected a rare large deletion removing exon 4 to exon 10 of the PKLR gene in the mother. Gap-PCR mapping confirmed that it to be a deletion previously found in a Vietnamese family (Costa C et al Haematologica 2005) and an Australian family (Fermo E et al Br J Haematol 2005). Both mutations have not been previously reported in Chinese. The proband was found to carry the paternal point mutation and the maternal deletion. Because of the severe clinical course of their first child, the couple requested prenatal biopsy was performed at 12 week of gestation. The fetus was found to be simple heterozygous for the paternal mutation. Pregnancy was allowed to continue and a healthy baby was born. A PK assay performed at the age of 9 months was normal. Mutation studies in a peripheral blood sample at 10 months of age confirmed the PKLR genotype. There was no evidence of hemolytic anemia after 3 years of follow up. Because of its perceived rarity and benignity in many ethnic groups, PK deficiency does not enter early into the differential diagnosis of anemia in pediatric patients. Its potential to cause severe disease is often overlooked and delay in diagnosis is common (Pissard S et al J Pediatr 2007). Genetic characterization and genotype-phenotype correlation studies on PKLR in different populations are indicated to better characterize the disease spectrum and to define the role of prenatal diagnosis in PK deficiency. Disclosures: No relevant conflicts of interest to declare.

Prenatal diagnosis of X-linked hydrocephalus in a Chinese family with four successive affected pregnancies

1994 ◽  
Vol 14 (1) ◽  
pp. 57-60 ◽  
Author(s):  
Tsang-Ming Ko ◽  
Hsiao-Ling Hwa ◽  
Li-Hui Tseng ◽  
Fon-Jou Hsieh ◽  
Shiu-Feng Huang ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Chinese Family

scholarly journals A Novel BBS9 Mutation Identified via Whole-Exome Sequencing in a Chinese Family with Bardet-Biedl Syndrome

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Yue Zhang ◽  
Manhong Xu ◽  
Minglian Zhang ◽  
Guoxing Yang ◽  
Xiaorong Li
Keyword(s):  
Mental Retardation ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Chinese Family ◽  
Cone Dystrophy ◽  
Bardet Biedl Syndrome ◽  
Homozygous Variant ◽  
Whole Exome

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder characterized by polydactyly, obesity, rod-cone dystrophy, and mental retardation. Twenty-one genes have been identified as causing BBS. This study collected a BBS pedigree from two patients and performed whole-exome sequencing on one patient. We identified a novel homozygous variant c.1114C>T (p.Q372X) in the BBS9 of the two siblings. This variant was confirmed and completely cosegregated with the disease of this family by Sanger sequencing. We report a novel homozygous variant c.1114C>T in the BBS9 gene in a Chinese family.

Mutation analysis and prenatal diagnosis in a Chinese family with succinic semialdehyde dehydrogenase and a systematic review of the literature of reported ALDH5A1 mutations

2016 ◽  
Vol 44 (4) ◽  
Author(s):  
Ning Liu ◽  
Xiang-dong Kong ◽  
Quan-cheng Kan ◽  
Hui-rong Shi ◽  
Qing-hua Wu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Prenatal Diagnosis ◽  
Genetic Analysis ◽  
Aminobutyric Acid ◽  
Chinese Family ◽  
Succinic Semialdehyde ◽  
Review Of The Literature ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Semialdehyde Dehydrogenase ◽  
Ssadh Deficiency

AbstractSuccinic semialdehyde dehydrogenase (SSADH) deficiency is a neurometabolic disease in which the degradation of γ-aminobutyric acid (GABA) is impaired. The purpose of this study was to report two novelGenetic analysis ofTwo novel

scholarly journals Mutation detection and prenatal diagnosis of XLHED pedigree

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3691 ◽  
Author(s):  
Yao Lin ◽  
Wei Yin ◽  
Zhuan Bian
Keyword(s):  
Prenatal Diagnosis ◽  
Structural Changes ◽  
Frameshift Mutation ◽  
Stop Codon ◽  
Direct Sequencing ◽  
Premature Stop Codon ◽  
Deciduous Teeth ◽  
Chinese Family ◽  
Female Carrier ◽  
Causative Gene

Background The phenotypic characters of X -linked Hypohidrotic Ectodermal Dysplasia (XLHED) are the dysplasia of epithelial- and mesenchymal-derived organs. Ectodysplasin (EDA) is the causative gene of XLHED. Methods The current study reported a large Chinese XLHED pedigree. The genomic DNA of adult and fetus was extracted from peripheral blood and shed chorion cell respectively. The nucleotide variation in EDA gene was screened through direct sequencing the coding sequence. The methylation state of EDA gene’s promoter was evaluated by pyrosequencing. Results This Chinese XLHED family had two male patients and three carriers. All of them were with a novel EDA frameshift mutation. The mutation, c.172-173insGG, which leads to an immediate premature stop codon in exon one caused severe structural changes of EDA. Prenatal diagnosis suggested that the fetus was a female carrier. The follow-up observation of this child indicated that she had mild hypodontia of deciduous teeth at age six. The methylation level of EDA gene’s promoter was not related to carriers’ phenotype changes in this family. Discussion We reported a new frameshift mutation of EDA gene in a Chinese family. Prenatal diagnosis can help to predict the disease status of the fetus.

Diagnosis and Prenatal Diagnosis in a Chinese Family Carrying the Rare α-Thalassemia Gene HBA2: c.1A>G Mutation

Hemoglobin ◽  
2020 ◽  
Vol 44 (1) ◽  
pp. 51-54
Author(s):  
Xingyuan Chen ◽  
Shiqiang Luo ◽  
Jun Huang ◽  
Dejian Yuan ◽  
Tizhen Yan ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Chinese Family
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