DOI: http://dx.doi.org/10.18203/2349-3291.ijcp20205102

Alymphoid cystic thymic dysgenesis - FOXN1 gene mutation: a rare case report of two siblings

Abdus Subhan Sohail, Vidya Krishnamurthy, Hareesh Sanikam, Pushpalatha Kariyappa, Udayakumar Seetharam Rao

Abstract


Alymphoid cystic thymic dysgenesis is a severe combined immunodeficiency (SCID) syndrome caused b y   a   mutation   in fork head box N1 gene (FOXN1) on chromosome 17. It is a transcriptional factor regulating the development, differentiation and function of thymic epithelial cells; maintaining T-lineage progenitors in bone marrow; promoting terminal differentiation of epithelial cells of hair follicles. Mutation in FOXN1 is known to cause a rare disorder characterized by rudimentary thymus gland (primary lymphoid organ for T-cell differentiation), T-cell immunodeficiency, congenital alopecia totalis and nail dystrophy. Here we report two affected siblings from a non-consanguineous family with similar features of alopecia totalis, nail dystrophy and failure to thrive. The first child was a 7-month-old female baby, with history of two hospitalization in the past for lower respiratory tract infection, had left axillary lymphadenopathy (BCG adenitis), alopecia totalis, nail dystrophy and hepatosplenomegaly. Bronchoalveolar lavage secretion was positive for Mycobacterium tuberculosis and Pneumocystis carinii pneumonia by gene Xpert and polymerase chain reaction respectively. Immunodeficiency panel workup revealed combined T cell and B cell immunodeficiency, genetic analysis by whole exome sequencing revealed   recessive missense mutation in exon 6 of FOXN1 gene on chromosome 17. Due to lack of sufficient literature it was reported as variant of unknown significance and to establish its clinical significance the carrier status of both the parents was established. Second child presented to us at 3 months of age, also had similar phenotypic features and on evaluation had very low lymphocyte subset count however mutational analysis could not be done in this child due to parent’s denial. Hence, we conclude this child also was affected.


Keywords


Alymphoid cystic thymic dysgenesis, SCID, FOXN1, Alopecia, Nail dystrophy

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References


Flanagan SP. 'Nude', a new hairless gene with pleiotropic effects in the mouse. Genet Res. 1966;8(3):295-309.

Nehls M, Pfeifer D, Schorpp M, Hedrich H, Boehm T. New member of the winged-helix protein family disrupted in mouse and rat nude mutations. Nature. 1994;372(6501):103-7.

Pignata C, Fiore M, Guzzetta V, Castaldo A, Sebastio G, Porta F, et al. Congenital Alopecia and nail dystrophy associated with severe functional T-cell immunodeficiency in two sibs. Am J Med Genet. 1996;65(2):167-70.

Rota IA, Dhalla F. FOXN1 deficient nude severe combined immunodeficiency. Orphanet J Rare Dis. 2017;12:6.

Adriani M, Martinez-Mir A, Fusco F, Busiello R, Frank J, Telese S, et al. Ancestral founder mutation of the nude (FOXN1) gene in congenital severe combined immunodeficiency associated with alopecia in southern Italy population. Ann Hum Genet. 2004;68(Pt 3):265-8.

Radha Rama Devi A, Panday NN, Naushad SM. FOXN1 Italian founder mutation in Indian family: Implications in prenatal diagnosis. Gene. 2017;627:222-5.

Amorosi S, D'Armiento M, Calcagno G, Russo I, Adriani M, Christiano AM, et al. FOXN1 homozygous mutation associated with anencephaly and severe neural tube defect in human athymic Nude/SCID fetus. Clin Genet. 2008;73(4):380-4.

Amorosi S, Vigliano I, Del Giudice E, Panico L, Maruotti GM, Fusco A, Quarantelli M, Ciccone C, Ursini MV, Martinelli P, Pignata C. Brain alteration in a Nude/SCID fetus carrying FOXN1 homozygous mutation. J Neurol Sci. 2010;298(1-2):121-3.

Chou J, Massaad MJ, Wakim RH, Bainter W, Dbaibo G, Geha RS. A novel mutation in FOXN1 resulting in SCID: a case report and literature review. Clin Immun. 2014;155(1):30-2.

Markert ML, Marques JG, Neven B, Devlin BH, McCarthy EA, Chinn IK, et al. First use of thymus transplantation therapy for FOXN1 deficiency (nude/SCID): a report of 2 cases. Blood. 2011;117(2):688-96.