A novel single point mutation of the LYST gene in two siblings with different phenotypic features of Chediak Higashi syndrome

Abstract

Chediak Higashi syndrome (CHS) is an autosomal-recessive disorder characterized by oculocutaneous albinism, recurrent infections and a progressive primary neurological disease. Here, we describe two siblings with CHS due to a novel homozygous R1836X mutation in the LYST gene associated with loss of NK cell degranulation and cytotoxicity. While one sibling was born with fair skin and hair and died of hemophagocytic lymphohistiocytosis (HLH) at 5 months of age, the other sibling had dark black hair and skin and developed HLH at the age of 4 years.

Prognostic Factors and Long-Term Outcome in 52 Turkish Children With Hemophagocytic Lymphohistiocytosis*

“…However, chronic intractable diarrhea since birth has not been described in other patients with STXBP2 mutation. Two siblings with HLH associated with CHS were previously reported by Kaya et al (28). Both of them did not have suitable stem cell donor and eventually died, confirming the previous observations that patients with IDHLH who achieved limited benefit from HLH protocol should be transplanted as soon as possible after diagnosis (28,29).…”

Malignancies in Primary Immunodeficiencies: A Single Center Experience

“…28 The presented patient with CHS suffered HLH attack on two occasions. She was hospitalized with hepatosplenomegaly and fever when she was 3 years old.…”

Subtle differences in CTL cytotoxicity determine susceptibility to hemophagocytic lymphohistiocytosis in mice and humans with Chediak-Higashi syndrome

“…Moreover, 2 examples of siblings with a divergent clinical phenotype have been reported. 26,39,40 This is not unexpected because the time of onset of HLH is not exclusively determined genetically but also by environmental factors, such as triggering infections. The observation of different CTL cytotoxicity, CTL degranulation, and a different pigmentation phenotype 26 in 2 siblings with the same mutation is more difficult to explain.…”

“…Interestingly, P4 and P9 were siblings carrying the same homozygous truncating mutation but differed significantly in their clinical presentation. 26 Overall, there was no genotype-phenotype correlation, and the clinical course could not be predicted by the nature of the mutations.…”