Accelerated phase development in a late-onset adolescent Chediak-Higashi syndrome patient caused by compound novel LYST mutations in the setting of SARS-CoV-2 infection

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive genetic disorder characterized by severe immunodeficiency, albinism and coagulation deficiency. Mostly diagnosed in early childhood, this devastating condition is associated with lysosomal abnormalities attributed to the absence or impaire...

Full description

Saved in:
Bibliographic Details
Published inBlood cells, molecules, & diseases Vol. 109; p. 102874
Main Authors Guo, Ping, Wu, Xi, Yang, Mingkang, Xue, Yilun, Zhou, Jiakuan, Huang, Zhixi, Wu, Wenman, Wang, Jianbiao
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.11.2024
Subjects
Adolescent
Chediak-Higashi syndrome
Chediak-Higashi Syndrome - diagnosis
Chediak-Higashi Syndrome - genetics
CHS1/LYST
COVID-19 - complications
COVID-19 - genetics
Female
Hemophagocytic lymphohistiocytosis
Humans
Male
Mutation
SARS-CoV-2
SARS-CoV-2 - genetics
Vesicular Transport Proteins - genetics
CHS1/LYST
Hemophagocytic lymphohistiocytosis
SARS-CoV-2
Chediak-Higashi syndrome
Online AccessGet full text

Cover

More Information
Summary:Chediak-Higashi syndrome (CHS) is a rare autosomal recessive genetic disorder characterized by severe immunodeficiency, albinism and coagulation deficiency. Mostly diagnosed in early childhood, this devastating condition is associated with lysosomal abnormalities attributed to the absence or impaired function of lysosomal trafficking regulator caused by mutations in the CHS1/LYST gene. In current study, we report a case of late-onset CHS caused by two novel compound heterozygous CHS1/LYST mutations: c.8407C > T, leading to early termination of translation at residue Gln2803 (p. Gln2803Ter), and a small deletion c. 4020_4031del, resulting in an in-frame deletion of three amino acid residues (p. Asp1343_Val1346del). Both variants retain a large part of the CHS/LYST protein, particularly p. Asp1343_Val1346del, which preserves critical functional BEACH and WD40 domains in the C terminal, potentially maintaining residual activity and alleviating patient symptoms. The timeline of SARS-CoV-2 infection and rapid symptom progression suggests that the viral infection may have trigger the accelerated phase development leading to a poor prognosis.
Bibliography:ObjectType-Case Study-2
SourceType-Scholarly Journals-1
ObjectType-Feature-4
content type line 23
ObjectType-Report-1
ObjectType-Article-3
ISSN:1079-9796
1096-0961
1096-0961
DOI:10.1016/j.bcmd.2024.102874