Rapid genome sequencing identifies novel variants in complement factor I

Katherine M Rodriguez; Jordan Vaught; Michelle Dilley; Kataryzna Ellsworth; Alaina Heinen; Edsel M Abud; Yuzhou Zhang; Richard J H Smith; Robert Sheets; Bob Geng; Hal M Hoffman; H Michael Worthen; David Dimmock; Nicole G Coufal

doi:10.1101/mcs.a006239

Rapid genome sequencing identifies novel variants in complement factor I

Cold Spring Harb Mol Case Stud. 2022 Dec 28;8(7):a006239. doi: 10.1101/mcs.a006239. Print 2022 Dec.

Authors

Katherine M Rodriguez^#^{1

2

3}, Jordan Vaught^#^{1

4}, Michelle Dilley^{1

5}, Kataryzna Ellsworth³, Alaina Heinen³, Edsel M Abud^{5

6}, Yuzhou Zhang⁷, Richard J H Smith⁷, Robert Sheets^{1

5}, Bob Geng^{1

5}, Hal M Hoffman^{1

5}, H Michael Worthen^{1

2}, David Dimmock³, Nicole G Coufal^{1

2

3}

Affiliations

¹ Rady Children's Hospital, San Diego, California 92123, USA.
² Division of Pediatric Critical Care, Department of Pediatrics, University of California at San Diego, San Diego, California 92123, USA.
³ Rady Children's Institute for Genomic Medicine, San Diego, California 92123, USA.
⁴ Department of Pediatrics, Immunology, and Rheumatology, Department of Pediatrics, University of California at San Diego, San Diego, California 92161, USA.
⁵ Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, University of California at San Diego, San Diego, California 92161, USA.
⁶ Division of Allergy, Asthma, and Immunology, Scripps Clinic, San Diego, California 92093, USA.
⁷ Molecular Otolaryngology and Renal Research Laboratories, University of Iowa, Iowa City, Iowa 52242, USA.

^# Contributed equally.

Abstract

Complement factor I deficiency (CFID; OMIM #610984) is a rare immunodeficiency caused by deficiencies in the serine protease complement factor I (CFI). CFID is characterized by predisposition to severe pneumococcal infection, often in infancy. We report a previously healthy adolescent male who presented with respiratory failure secondary to pneumococcal pneumonia and severe systemic inflammatory response. Rapid genome sequencing (rGS) identified compound heterozygous variants in CFI in the proband, with a novel maternally inherited likely pathogenic variant, a single nucleotide deletion resulting in premature stop (c.1646del; p.Asn549ThrfsTer25) and a paternally inherited novel likely pathogenic deletion (Chr 4:110685580-110692197del).

Keywords: ST segment elevation; atelectasis; cough; elevated C-reactive protein level; elevated serum transaminases during infections; exudative pleural effusion; hyponatremia; lymphopenia; myocarditis; nausea; normocytic anemia; respiratory failure; sinus tachycardia; tension-type headache; unexplained fevers.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adolescent
Chromosome Mapping
Complement Factor I*
Genotype
Humans
Male

Substances

Complement Factor I

Abstract

Publication types

MeSH terms

Substances

Grants and funding