Variant Type X91+ Chronic Granulomatous Disease: Clinical and Molecular Characterization in a Chinese Cohort

We present two rare cases of p67phox-deficient chronic granulomatous disease (CGD) caused by compound heterozygous mutations in the NCF2 gene. They developed cervical lymphadenitis as the initial manifestation of CGD but had distinct clinical progressions. Patient 1 presented with aspergillous meningitis, an extremely rare manifestation of neurological involvement in CGD, which has not been reported before. Patient 2 presented with non-infectious inflammatory lymphadenitis is also very rare and has not been reported previously. These cases emphasize the importance of considering p67phox-deficient CGD in children with late-onset invasive fungal infections and non-infectious inflammatory lesions. Additionally, we also reviewed previous reports of Chinese patients with P67phox-Deficient CGD. Our objective is to raise awareness about the clinical, diagnostic, and genetic characteristics of P67phox-deficient CGD in China, to reduce misdiagnosis and improve the management and prognosis of the disease.

show abstract

Dual novel homozygous mutations in ISG15 and MPO lead to classic type I interferonopathy and a new phenotype of recurrent parenchymal pneumonia

Xu¹,

Li²,

zhao³

et al. 2022

Preprint

View full text Add to dashboard Cite

Purpose ISG15 deficiency, a rare human inborn error of immunity characterized by susceptibility to Mycobacterium tuberculosis infection, shows neuropathic and dermatological manifestations. MPO deficiency is a common inherited defect of phagocytes, but it is not classified as an independent primary immune deficiency due to lack of clinical symptoms. Dual mutation of ISG15 and MPO has not been reported. Methods We analyzed the clinical, genetic, and immunological features of two siblings with ISG15 deficiency combined with MPO mutations, and explored therapeutic candidates. Results The major manifestation observed in patient 2 was necrotic skin lesions, while those in patient 1 were intracranial calcification and recurrent pneumonia. Whole-exome sequencing indicated novel, dual mutations in ISG15 and MPO, leading to lack of ISG15 expression and reduced MPO expression. PBMCs and B-cell lines derived from the patients showed hyperactivated JAK/STAT signaling and elevated oxidative stress. A "False-Positive" DHR test for MPO was reversed by exogenous peroxidase. RNA sequencing analyses identified baricitinib as an available therapeutic candidate for hyper-inflammation associated with ISG15 deficiency. Conclusions We reported two sibling patients with the same novel ISG5 mutation combined with partial MPO deficiency. These patients showed different presentations, and one of them harbored a new phenotype of recurrent pneumonia. These findings expand the clinical spectrum of ISG15 deficiency, reinforce its diversity, and identify a potential therapeutic candidate for this rare disease.

show abstract

Variant Type X91+ Chronic Granulomatous Disease: Clinical and Molecular Characterization in a Chinese Cohort

Cited by 3 publications

References 65 publications

A novel homozygous Y140X mutation of ISG15 causes diverse type I interferonopathies in sibling patients with cutaneous lesions or recurrent parenchymal pneumonia

A novel homozygous Y140X mutation of ISG15 causes diverse type I interferonopathies in sibling patients with cutaneous lesions or recurrent parenchymal pneumonia

Two distinct clinical progressions of P67phox-deficient CGD, both commencing with cervical lymphadenitis

Dual novel homozygous mutations in ISG15 and MPO lead to classic type I interferonopathy and a new phenotype of recurrent parenchymal pneumonia

Contact Info

Product

Resources

About