Ann Lab Med.  2021 Mar;41(2):207-213. 10.3343/alm.2021.41.2.207.

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

• Seo JY
• Ahn JY
• Keam B
• Kim M
• Yoon S
• Lee JL
• Park K
• Park I

• KMID: 2512667
• DOI: http://doi.org/10.3343/alm.2021.41.2.207

Abstract

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.

Keyword

FH; Genotype; Hereditary leiomyomatosis and renal cell cancer; Korean; Novel variant; Phenotype

Figure

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  Fig. 1 Distribution of FH variants identified in this study.

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  Fig. 2 Pedigree of P1 harboring the c.1108+1G > A variant (indicated by arrow). All three sisters of P1 who are carriers of the c.1108+1G > A variant underwent a hysterectomy before the age of 40 years. FH genetic testing was not performed for the son of the third sister. P1’s older brother was asymptomatic at the time of genetic testing. Abbreviations: Ut, uterine; Cut, cutaneous.

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