Genetic variants of the APE1 gene and the risk of vitiligo in a Chinese population: A genotype–phenotype correlation study

Abstract Background Charcot–Marie–Tooth (CMT) disease is an exciting field of study, with a growing number of causal genes and an expanding phenotypic spectrum. The microrchidia family CW-type zinc finger 2 gene (MORC2) was newly identified as a causative gene of CMT2Z in 2016. We aimed to describe the phenotypic-genetic spectrum of MORC2-related diseases in the Chinese population. Methods With the use of Sanger sequencing and Next Generation Sequencing (NGS) technologies, we screened a cohort of 284 unrelated Chinese CMT2 families. Pathogenicity assessments of MORC2 variants were interpreted according to the ACMG guidelines. Potential pathogenic variants were confirmed by Sanger sequencing. Results We identified 4 different heterozygous MORC2 mutations in four unrelated families, accounting for 1.4% (4/284). A novel mutation c.1397A>G p. D466G was detected in family 1 and all affected patients presented with later onset axonal CMT with hyperCKemia. The patient in family 2 showed a spinal muscular atrophy (SMA)-like disease with cerebellar hypoplasia and mental retardation, with a hot spot de novo mutation c.260C>T p. S87L. The twin sisters in family 3 were identified as having the most common mutation c.754C>T p. R252W and suffered from axonal motor neuropathy with high variability in disease severity and duration. The patient in family 4 developed an early onset axonal motor and sensory neuropathy, with a reported mutation c.1220G>A p.C407Y. All identified mutations associated with MORC2-related neuropathies are localized in the N-terminal ATPase module. Conclusions Our study confirmed that MORC2-related neuropathies exist in the Chinese population at a relatively high mutation rate. We revealed a complex genotype–phenotype correlation with MORC2 mutations. This report adds a new piece to the puzzle of the genetics of CMT and contributes to a better understanding of the disease mechanisms.

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Loss of succinate dehydrogenase subunit B (SDHB) expression is limited to a distinctive subset of gastric wild-type gastrointestinal stromal tumours: a comprehensive genotype–phenotype correlation study

Yearbook of Pathology and Laboratory Medicine ◽

10.1016/j.ypat.2012.10.009 ◽

2013 ◽

Vol 2013 ◽

pp. 143-144

Author(s):

S.S. Raab

Keyword(s):

Succinate Dehydrogenase ◽

Correlation Study ◽

Wild Type ◽

Gastrointestinal Stromal Tumours ◽

Phenotype Correlation ◽

Genotype Phenotype Correlation ◽

Succinate Dehydrogenase Subunit B ◽

Subunit B

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Neonatal Screening and Genotype-Phenotype Correlation of 21-Hydroxylase Deficiency in the Chinese Population

Frontiers in Genetics ◽

10.3389/fgene.2020.623125 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xin Wang ◽

Yanyun Wang ◽

Dingyuan Ma ◽

Zhilei Zhang ◽

Yahong Li ◽

...

Keyword(s):

Neonatal Screening ◽

Chinese Population ◽

Eastern China ◽

Laboratory Data ◽

Adrenal Crisis ◽

Molecular Characteristics ◽

Phenotype Correlation ◽

Hydroxylase Deficiency ◽

Genotype Phenotype Correlation ◽

21 Hydroxylase Deficiency

Background: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders encompassing enzyme deficiencies in the adrenal steroidogenesis pathway that leads to impaired cortisol biosynthesis. 21-hydroxylase deficiency (21-OHD) is the most common type of CAH. Severe cases of 21-OHD may result in death during the neonatal or infancy periods or sterility in later life. The early detection and timely treatment of 21-OHD are essential. This study aimed to summarize the clinical and genotype characteristics of 21-OHD patients detected by neonatal screening in Nanjing, Jiangsu province of China from 2000 to 2019.Methods: Through a retrospective analysis of medical records, the clinical presentations, laboratory data, and molecular characteristics of 21-OHD patients detected by neonatal screening were evaluated.Results: Of the 1,211,322 newborns who were screened, 62 cases were diagnosed with 21-OHD with an incidence of 1:19858. 58 patients were identified with the classical salt-wasting type (SW) 21-OHD and four patients were identified with simple virilizing type (SV) 21-OHD. Amongst these patients, 19 cases patients accepted genetic analysis, and another 40 cases were received from other cities in Eastern China. Eighteen different variants were found in the CYP21A2 gene. The most frequent variants was c.293-13A/C>G (36.29%). The most severe clinical manifestations were caused by large deletions or conversions of CYP21A2.Conclusions: This study suggested that neonatal screening effectively leads to the early diagnosis of 21-OHD and reduces fatal adrenal crisis. Our data provide additional information on the occurrence and genotype-phenotype correlation of 21-OHD in the Chinese population which can be used to better inform treatment and improve prognosis.

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