for our NEMO families

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This is an abstract being presented at the AAAAI conference right now in New

Orleans

J ALLERGY CLIN IMMUNOL

FEBRUARY 2010

AB76 Abstracts

SUNDAY

302 Congenital NEMO Alteration at Position 223 causes Ectodermal Dysplasia and

Immunodeficiency with

Normogammaglobulinemia

G. Karamchandani-Patel1, R. U. Sorensen1, E. Hanson2, R. Saltzman2,

J. Orange2; 1Louisiana State University Health Sciences Center, New Orleans,

LA, 2University of Pennsylvania School of Medicine, Philadelphia,

PA.

RATIONALE: Hypomorphic mutations in the NEMO gene result in

a variable syndrome of somatic and immunological abnormalities. It is

becoming increasingly apparent that there are clinically relevant genotype-

phenotype associations in this disease. We studied two unrelated

boys with novel NEMO mutations resulting in alterations at position 223

to determine if they had similar phenotypes.

METHODS: Clinical and immunologic characteristics as well as NF-kB

activation were defined in two patients with novel NEMO mutations predicted

to affect residue 223. Since this specific region of theNEMOprotein

has not been previously affected, consideration was given to a new genotype-

phenotype correlation.

RESULTS: Both patients were diagnosed at age two with hypohydrotic

ectodermal dysplasia. Immunoglobulin levels, lymphocyte subpopulations

and lymphocyte proliferation studies were normal. Patient 1 had recurrent

sinopulmonary infections and pneumococcal antibody titers protective to

only 1/14 serotypes. Patient 2 had a necrotizing soft tissue MRSA infection

at 16 months and streptococcal angiosus bacteremia with subdural empyema

at 26 months.

DNA sequencing of the NEMO gene in both patients revealed mutations in

exon 5 corresponding to position 223. Patient 1 had a 3 nucleotide deletion,

c.667_669delGAG predicting the deletion of glutamine 223. Patient 2 had

a missense mutation resulting in a nucleotide 667G>A which predicts

Glu223>Lys substitution. Infectious susceptibility in both patients improved

after immunoglobulin replacement therapy.

CONCLUSIONS: Two different novel mutations affecting NEMO position

223 resulted in clinically relevant and similar phenotypes. This underscores

the consideration of genotype-phenotype correlations in this disease

and defines residue 223 as dispensable for quantitative, but not qualitative

immunoglobulin production. Ursula

Mom to (17) and Macey (14)

http://www.caringbridge.org/visit/maceyholleman