TY - JOUR
T1 - Immunologic Heterogeneity in 2 Cartilage-Hair Hypoplasia Patients With a Distinct Clinical Course
AU - Gamliel, A.
AU - Lee, Y. N.
AU - Lev, A.
AU - Abuzaitun, O.
AU - Rechavi, E.
AU - Levy, S.
AU - Simon, A. J.
AU - Somech, R.
N1 - Publisher Copyright:
© 2023 Esmon Publicidad.
PY - 2023
Y1 - 2023
N2 - Introduction: Cartilage-hair hypoplasia (CHH) syndrome is a rare autosomal recessive syndrome associated with skeletal dysplasia, varying degrees of combined immunodeficiency (CID), short stature, hair hypoplasia, macrocytic anemia, increased risk of malignancies, and Hirschsprung disease. Purpose: To provide clinical and immunological insights obtained from 2 unrelated patients who displayed clinical characteristics of CHH. Methods: Two patients with suspected CHH syndrome due to skeletal dysplasia and immunodeficiency underwent an immunological and genetic work-up using flow cytometry, next-generation sequencing (NGS) of the immune repertoire, and Sanger sequencing to identify the underlying defects. Results: Patient 1 presented with low birth weight and skeletal dysplasia. Newborn screening was suggestive of T-cell immunodeficiency, as T-cell receptor excision circle levels were undetectable. Both the T-cell receptor (TCR) Vß and TCR-g (TRG) repertoires were restricted, with evidence of clonal expansion. Genetic analysis identified compound heterozygous RMRP variants inherited from both parents. Patient 2 presented with recurrent lung and gastrointestinal infections, skeletal dysplasia, failure to thrive, and hepatomegaly. The polyclonal pattern of the TCRß repertoire was normal, with only slight overexpression of TCR-ßV20 and restricted expression of Vßs. TRG expressed a normal diverse repertoire, similar to that of the healthy control sample. Genetic analysis identified biallelic novel regulatory variants in RMRP. Both parents are carriers of this mutation. Conclusion: Our findings demonstrate how the immunological work-up, supported by genetic findings, can dramatically change treatment and future outcome in patients with the same clinical syndrome.
AB - Introduction: Cartilage-hair hypoplasia (CHH) syndrome is a rare autosomal recessive syndrome associated with skeletal dysplasia, varying degrees of combined immunodeficiency (CID), short stature, hair hypoplasia, macrocytic anemia, increased risk of malignancies, and Hirschsprung disease. Purpose: To provide clinical and immunological insights obtained from 2 unrelated patients who displayed clinical characteristics of CHH. Methods: Two patients with suspected CHH syndrome due to skeletal dysplasia and immunodeficiency underwent an immunological and genetic work-up using flow cytometry, next-generation sequencing (NGS) of the immune repertoire, and Sanger sequencing to identify the underlying defects. Results: Patient 1 presented with low birth weight and skeletal dysplasia. Newborn screening was suggestive of T-cell immunodeficiency, as T-cell receptor excision circle levels were undetectable. Both the T-cell receptor (TCR) Vß and TCR-g (TRG) repertoires were restricted, with evidence of clonal expansion. Genetic analysis identified compound heterozygous RMRP variants inherited from both parents. Patient 2 presented with recurrent lung and gastrointestinal infections, skeletal dysplasia, failure to thrive, and hepatomegaly. The polyclonal pattern of the TCRß repertoire was normal, with only slight overexpression of TCR-ßV20 and restricted expression of Vßs. TRG expressed a normal diverse repertoire, similar to that of the healthy control sample. Genetic analysis identified biallelic novel regulatory variants in RMRP. Both parents are carriers of this mutation. Conclusion: Our findings demonstrate how the immunological work-up, supported by genetic findings, can dramatically change treatment and future outcome in patients with the same clinical syndrome.
KW - Cartilage-Hair Hypoplasia (CHH)
KW - NGS
KW - RMRP
KW - Severe combined immunodeficiency (SCID)
KW - TCR repertoire
UR - http://www.scopus.com/inward/record.url?scp=85148765080&partnerID=8YFLogxK
U2 - 10.18176/jiaci.0792
DO - 10.18176/jiaci.0792
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C2 - 35166674
AN - SCOPUS:85148765080
SN - 1018-9068
VL - 33
SP - 263
EP - 270
JO - Journal of Investigational Allergology and Clinical Immunology
JF - Journal of Investigational Allergology and Clinical Immunology
IS - 4
ER -