Clinical staging and genetic profiling of Korean patients with primary lymphedema using targeted gene sequencing

• Published in: Scientific reports Vol. 12; no. 1; p. 13591
• Main Authors: Seo, Soo Hyun, Lee, Seungjun, Park, Joseph Kyu-hyung, Yang, Eun Joo, Kim, Boram, Lee, Jee-Soo, Kim, Man Jin, Park, Sung Sup, Seong, Moon-Woo, Nam, Sun-Young, Heo, Chan-Yeong, Myung, Yujin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10-08-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208; 631/443; 692/420; 692/53; Extremities; Humanities and Social Sciences; Lymphedema; multidisciplinary; Next-generation sequencing; Patients; Phenotypes; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-17958-7

Lymphedema is a progressive disease caused by lymphatic flow blockage in the lymphatic pathway. Primary (hereditary) lymphedema is caused by genetic mutations without secondary causes. We performed clinical profiling on Korean primary lymphedema patients based on their phenotypes using lymphoscintigraphy and made genetic diagnoses using a next-generation sequencing panel consisting of 60 genes known to be related to primary lymphedema and vascular anomalies. Of 27 patients included in this study, 14.8% of the patients had lymphedema of the upper extremities, 77.8% had lymphedema of the lower extremities and 7.4% had 4-limbs lymphedema. Based on the International Society of Lymphology staging, 14, 10, and 3 patients had stage 3, 2, and 1 lymphedema, respectively. Only one family was genetically confirmed to harbor likely pathogenic variants in
CELSR1.
The proband was carrying two likely pathogenic variants in
CELSR1
, while her symptomatic mother was confirmed to carry only one of the variants. Furthermore, two other variants of uncertain significance in
CELSR1
were detected in other patients, making
CELSR1
the most commonly altered gene in our study. The clinical and genetic profile of hereditary lymphedema reported here is the first such data series reported for South Korea.