Prenatal diagnosis of citrullinemia type 1: A Chinese family with a novel mutation of the ASS1 gene

Abstract Recessive congenital methemoglobinemia due to nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase (b5R) deficiency is classified into 2 clinical types: type 1 (erythrocyte type) and type 2 (generalized type). We found a Chinese family with type 1 recessive congenital methemoglobinemia, the patients from which were diagnosed according to clinical symptoms and b5R enzyme activity in the blood cells. To learn the molecular basis of type 1 recessive congenital methemoglobinemia in this Chinese family, we isolated total RNA from the peripheral leukocytes of the propositus and b5R complementary DNA (cDNA) by reverse transcription– polymerase chain reaction (RT-PCR). The coding region of the b5R cDNA was analyzed by sequencing the cloned PCR products. The results showed that the propositus was homozygous for a G→A transition at codon 203 in exon 7, changing a cysteine to a tyrosine (Cys203Tyr). To characterize the mutant enzyme, both glutathione S-transferase (GST)-fused wild-type b5R and GST-fused mutant Cys203Tyr b5R were expressed in Escherichia coli and affinity purified. The results showed that the catalytic activity of the enzyme was not much affected by this amino acid substitution, but the mutant enzyme exhibited decreased heat stability and increased susceptibility to trypsin. These properties of the mutant enzyme would account for the restricted b5R deficiency and mild clinical manifestations of these type 1 patients. The finding of this novel mutation makes codon 203 the only position within the b5R gene at which more than 1 mutation has been found.

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A novel mutation in the MYO7A gene is associated with Usher syndrome type 1 in a Chinese family

International Journal of Pediatric Otorhinolaryngology ◽

10.1016/j.ijporl.2017.05.021 ◽

2017 ◽

Vol 99 ◽

pp. 40-43 ◽

Cited By ~ 1

Author(s):

Xiaoguang He ◽

Qi Peng ◽

Siping Li ◽

Pengyuan Zhu ◽

Chunqiu Wu ◽

...

Keyword(s):

Novel Mutation ◽

Usher Syndrome ◽

Chinese Family ◽

Syndrome Type ◽

Usher Syndrome Type

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Case Report: A Novel PAX3 Mutation Associated With Waardenburg Syndrome Type 1

Frontiers in Genetics ◽

10.3389/fgene.2021.609040 ◽

2021 ◽

Vol 12 ◽

Author(s):

Qiuming Hu ◽

Huazhong Ma ◽

Jiawei Shen ◽

Zongming Zhuang ◽

Jianqiang Li ◽

...

Keyword(s):

Case Report ◽

Genetic Test ◽

Novel Mutation ◽

Present Report ◽

Hereditary Disease ◽

Chinese Family ◽

Syndrome Type ◽

Waardenburg Syndrome ◽

Whole Exome

Background: Waardenburg Syndrome Type 1 (WS1) is a rare hereditary disease, which is usually caused by the mutations of PAX3 (paired box 3). Here, we reported a pedigree with WS1, which was caused by a novel mutation in PAX3.Case Report: In this present report, a 10-year-old boy and his twin sister from a Han Chinese family presented with iris pigmentary abnormality, synophrys, and broad and high nasal root. Their father presented premature whitening of the hair, but no iris pigmentary abnormality. Their aunts presented the same clinical characteristics with the twins and premature graying of hair. However, none of the patients reported hearing loss. The clinical diagnosis of the four patients from this pedigree was WS1. The whole exome sequencing (WES) revealed a novel mutation (c.959-5T>G) in the PAX3 gene, which could be responsible for the observed pathogenic of WS1 in this pedigree. The genetic test confirmed the diagnosis of WS1 in the four patients from the studied pedigree.Conclusion: This present study demonstrated that genetic test based on WES, an effective alternative to regular clinical examinations, helps diagnose WS1. The newly identified PAX3 gene mutation can expand the understanding of WS1.

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Identification of a novel mutation in POU3F4 for prenatal diagnosis in a Chinese family with X-linked nonsyndromic hearing loss

Journal of Genetics and Genomics ◽

10.1016/s1673-8527(09)60096-5 ◽

2010 ◽

Vol 37 (12) ◽

pp. 787-793 ◽

Cited By ~ 16

Author(s):

Jianzhong Li ◽

Jing Cheng ◽

Yanping Lu ◽

Yu Lu ◽

Aiting Chen ◽

...

Keyword(s):

Hearing Loss ◽

Prenatal Diagnosis ◽

Novel Mutation ◽

Chinese Family ◽

Nonsyndromic Hearing Loss

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A novel mutation in the NADH-cytochrome b5 reductase gene of a Chinese patient with recessive congenital methemoglobinemia

Blood ◽

10.1182/blood.v95.10.3250.010k23_3250_3255 ◽

2000 ◽

Vol 95 (10) ◽

pp. 3250-3255 ◽

Cited By ~ 1

Author(s):

Yao Wang ◽

Yu-Shui Wu ◽

Pei-Zhen Zheng ◽

Wen-Xi Yang ◽

Guo-An Fang ◽

...

Keyword(s):

Clinical Symptoms ◽

Novel Mutation ◽

Cytochrome B5 ◽

Clinical Manifestations ◽

Mutant Enzyme ◽

Chinese Family ◽

Coding Region ◽

Cytochrome B5 Reductase ◽

Nadh Cytochrome

Recessive congenital methemoglobinemia due to nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase (b5R) deficiency is classified into 2 clinical types: type 1 (erythrocyte type) and type 2 (generalized type). We found a Chinese family with type 1 recessive congenital methemoglobinemia, the patients from which were diagnosed according to clinical symptoms and b5R enzyme activity in the blood cells. To learn the molecular basis of type 1 recessive congenital methemoglobinemia in this Chinese family, we isolated total RNA from the peripheral leukocytes of the propositus and b5R complementary DNA (cDNA) by reverse transcription– polymerase chain reaction (RT-PCR). The coding region of the b5R cDNA was analyzed by sequencing the cloned PCR products. The results showed that the propositus was homozygous for a G→A transition at codon 203 in exon 7, changing a cysteine to a tyrosine (Cys203Tyr). To characterize the mutant enzyme, both glutathione S-transferase (GST)-fused wild-type b5R and GST-fused mutant Cys203Tyr b5R were expressed in Escherichia coli and affinity purified. The results showed that the catalytic activity of the enzyme was not much affected by this amino acid substitution, but the mutant enzyme exhibited decreased heat stability and increased susceptibility to trypsin. These properties of the mutant enzyme would account for the restricted b5R deficiency and mild clinical manifestations of these type 1 patients. The finding of this novel mutation makes codon 203 the only position within the b5R gene at which more than 1 mutation has been found.

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Prenatal diagnosis of Duchenne muscular dystrophy revealed a novel mosaic mutation in Dystrophin gene: a case report

BMC Medical Genetics ◽

10.1186/s12881-020-01157-0 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Yan Wang ◽

Yuhan Chen ◽

San Mei Wang ◽

Xin Liu ◽

Ya Nan Gu ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Sanger Sequencing ◽

De Novo ◽

Novel Mutation ◽

Neuromuscular Disorders ◽

Genetic Diagnosis ◽

Dystrophin Gene ◽

Chinese Family ◽

Heterozygous Mutation ◽

Dmd Gene

Abstracts Background Duchenne muscular dystrophies (DMDs) are X-linked recessive neuromuscular disorders with malfunction or absence of the Dystrophin protein. Precise genetic diagnosis is critical for proper planning of patient care and treatment. In this study, we described a Chinese family with mosaic DMD mutations and discussed the best method for prenatal diagnosis and genetic counseling of X-linked familial disorders. Methods We investigated all variants of the whole dystrophin gene using multiple DNA samples isolated from the affected family and identified two variants of the DMD gene in a sick boy and two female carriers by targeted next generation sequencing (TNGS), Sanger sequencing, and haplotype analysis. Results We identified the hemizygous mutation c.6794delG (p.G2265Efs*6) of DMD in the sick boy, which was inherited from his mother. Unexpectedly, a novel heterozygous mutation c.6796delA (p.I2266Ffs*5) of the same gene, which was considered to be a de novo variant, was detected from his younger sister instead of his mother by Sanger sequencing. However, further NGS analysis of the mother and her amniotic fluid samples revealed that the mother carried a low-level mosaic c.6796delA mutation. Conclusions We reported two different mutations of the DMD gene in two siblings, including the novel mutation c.6796delA (p.I2266Ffs*5) inherited from the asymptomatic mosaic-carrier mother. This finding has enriched the knowledge of the pathogenesis of DMD. If no mutation is detected in obligate carriers, the administration of intricate STR/NGS/Sanger analysis will provide new ideas on the prenatal diagnosis of DMD.

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