Novel <i>FH</i> mutation associated with multiple uterine leiomyomas in Chinese siblings

Zhao, Zichen; Wang, Wenhui; You, Yan; Zhu, Lan; Feng, Fengzhi

doi:10.1002/mgg3.1068

Cited by 4 publications

(4 citation statements)

References 14 publications

(15 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although Caucasian data have shown a high penetrance of cutaneous leiomyomas in HLRCC, such penetrance was less prevalent in Korean patients [ 5 , 6 , 8 , 13 ]. Similarly, cutaneous manifestations were absent in Japanese and Chinese HLRCC patients [ 15 - 17 ]. It is likely that the phenotypic spectrum of HLRCC differs between Asian and Caucasian populations.…”

Section: Discussionmentioning

confidence: 99%

Genotypic and Phenotypic Characteristics of Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome in Korean Patients

et al. 2021

View full text Add to dashboard Cite

Background Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant cancer predisposition syndrome. HLRCC is characterized by the development of cutaneous leiomyomas, early-onset uterine leiomyomas, and HLRCC-associated renal cell cancer (RCC) and caused by germline fumarate hydratase (FH) deficiency. We investigated the genotypic and phenotypic characteristics of Korean patients with HLRCC. Methods We performed direct sequencing analysis of FH in 13 patients with suspected HLRCC and their family members. A chromosomal microarray test was performed in female patients with negative sequencing results but highly suspected HLRCC. In addition, we analyzed the clinical characteristics and evaluated the genotype–phenotype correlations in Korean patients with HLRCC. Results We identified six different pathogenic or likely pathogenic FH variants in six of the 13 patients (46.2%). The variants included two nonsense variants, two splicing variants, one frameshift variant, and one missense variant. Of the six variants, two (33.3%) were novel (c.132+1G > C, and c.243dup). RCC and early-onset uterine leiomyoma were frequently observed in families with HLRCC, while cutaneous leiomyoma was less common. No significant genotype–phenotype correlation was observed. Conclusions We describe the genotypic and phenotypic spectrum in a small series of Korean patients with HLRCC. Our data reveal the unique characteristics of Korean patients with HLRCC and suggest a need for establishing an optimal diagnostic approach for them.

show abstract

Section: Discussionmentioning

confidence: 99%

Genotypic and Phenotypic Characteristics of Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome in Korean Patients

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Similarly, Jorge R. Toro et al reported that a shared mutation, R190H, was found among eleven distinct unrelated families of North America ( Toro et al, 2003 ). Zichen Zhao et al also investigated through their whole exome sequencing an unreported missense mutation in the FH gene (c.1214A>G, p. Leu405Ser) which was detected in both the patients and their father ( Zhao et al, 2020 ). The study summarized that alteration in FH gene may lead to leiomyoma cause.…”

Section: Methodsmentioning

confidence: 99%

Gene variants polymorphisms and uterine leiomyoma: an updated review

Upadhyay,

Dubey

2024

Front. Genet.

View full text Add to dashboard Cite

Uterine leiomyoma, commonly referred to as fibroids, is a benign tumor that develops in the muscular wall of the uterus. These growths are non-cancerous and can vary in size, ranging from tiny nodules to larger masses. Uterine leiomyomas often occur during a woman’s reproductive years and can lead to symptoms such as heavy menstrual bleeding, pelvic pain, and pressure on nearby organs. While the exact cause is not fully understood, hormonal factors, particularly estrogen and progesterone, are believed to play a role in their development. The exploration of connections between genetic variants and uterine leiomyoma has captivated scientific attention for numerous years. The results from investigations remain a subject of intrigue within the scientific community. To date, the findings regarding the relationships between single nucleotide polymorphisms (SNPs) and uterine leiomyoma have exhibited some inconsistencies. However, amidst these inconsistencies, several promising outcomes have emerged that hold the potential to shape future research endeavors. These promising leads could pave the way for the development of innovative targeted therapies and novel prognostic biomarkers. This review specifically centers on accentuating the existing literature data concerning genetic variants that have been explored for their potential connections to uterine leiomyoma. Additionally, it underscores the prospects of employing genetic variations as diagnostic and prognostic biomarkers for individuals diagnosed with uterine leiomyoma.

show abstract

“…Adrenal nodules and pheochromocytomas seem to be additional manifestations while further investigations would still be needed [ 3 , 4 , 5 ]. Cutaneous leiomyomas as one of the most common clinical features presented in over 80% of HLRCC patients, while studies implied that penetrance of cutaneous leiomyomas was low in Japanese, Korean, and Chinese HLRCC patients compared with Caucasians [ 6 , 7 ]. Females usually had uterine leiomyomas at the age of 30–50 years old, while females with HLRCC could develop multiple leiomyomas at a much younger age at 28–32 years old, with large and numerous myomas specifically [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

A Missense Mutation c.1132G > A in Fumarate Hydratase (FH) Leads to Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) Syndrome and Insights into Clinical Management in Uterine Leiomyomata

Shi

Chen

et al. 2023

Genes

View full text Add to dashboard Cite

Background: HLRCC syndrome is a hereditary cancer predisposition syndrome caused by heterozygous germline pathogenic variant of the fumarate hydratase (FH) gene and characterized by cutaneous leiomyomas (CL), uterine leiomyomas (UL), and renal cell carcinoma (RCC). Loss of function variant of FH gene inactivates the Kreb’s cycle enzyme activity and predisposes individuals with such variant to the development of HLRCC. Methods: Next-generation sequencing (NGS) and Sanger confirmation were given to family members accessible. Following that, a functional study in vitro was performed to further confirm the pathogenicity of the variant. FH-Wild type (FH-WT) and FH-mutant (FH-MUT) (E378K) plasmid were constructed and transfected into 293T and uterine leiomyoma cell lines, respectively. Proliferation assessment was executed to show how this mutation affects the growth of uterine leiomyoma. qPCR and Western blotting were performed to investigate the change of transcription and translation of FH with mutation (E378K), and FH enzyme assay activity were tested in 293T cells with mutation and wild-type plasmids. Results: Here, we presented two families with the same missense variant (c.1132G > A) that has not been reported as a germline mutation in hereditary uterine leiomyomas before and classified as VUS in gene databases. Our in vitro experiments supported the pathogenicity of this missense variant, especially in uterine leiomyomata. Conclusions: According to the American College of Medical Genetics (ACMG) guideline, the E378K variant was classified as likely pathogenic (with evidence PS4_support, PS3_support, PM2_support, PP1, PP3 and PP4 evidence). Further insights into clinical management in uterine leiomyomata were discussed and should be practiced in gynecological clinical settings.

show abstract

Novel FH mutation associated with multiple uterine leiomyomas in Chinese siblings

Cited by 4 publications

References 14 publications

Genotypic and Phenotypic Characteristics of Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome in Korean Patients

Genotypic and Phenotypic Characteristics of Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome in Korean Patients

Gene variants polymorphisms and uterine leiomyoma: an updated review

A Missense Mutation c.1132G > A in Fumarate Hydratase (FH) Leads to Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) Syndrome and Insights into Clinical Management in Uterine Leiomyomata

Contact Info

Product

Resources

About