Atypical presentation of Wiskott-Aldrich syndrome: diagnosis in two unrelated males based on studies of maternal T cell X chromosome inactivation [see comments]

Abstract

Congenital thrombocytopenia may occur in isolation or accompanied by eczema and immunodeficiency, as part of the X-linked hereditary Wiskott- Aldrich syndrome (WAS). Because the clinical and immunologic picture of WAS is variable, particularly early in life, definite diagnosis cannot always be made in cases with a negative family history. Two unrelated males with sporadic congenital thrombocytopenia had only questionable immunologic abnormalities as infants, making them clinically indistinguishable from cases of isolated thrombocytopenia, although one developed episodic neutropenia and the other began to manifest a multisystem autoimmune disease at 2 years of age. Evaluation of X chromosome inactivation in the T cells of both patients' mothers showed each of these women to have the same highly skewed X chromosome inactivation pattern seen in carriers of typical familial WAS. A T-cell defect was subsequently directly demonstrated in the second patient, whose lymphocytes failed to proliferate to periodate and anti-CD43. Taken together, these data suggest the presence of T cell immunodeficiency consistent with WAS in these patients. Furthermore, their mothers were found to have a very high likelihood of being carriers, lending support to the diagnosis of a hereditary disease in these boys and making possible genetic prediction in other family members and subsequent pregnancies.

From Mendel to mycoses: Immuno‐genomic warfare at the human–fungus interface

“…Severe Combined ImmunoDeficiency (SCID) CD45 311 Combined ImmunoDeficiency (CID) LCK 312 Severe Combined ImmunoDeficiency (SCID) ADA 313 CARD9 deficiency CARD9 290 IRF4 deficiency IRF4 314 LRBA deficiency LRBA 315 Activated PI3K-Delta Syndrome 1 PIK3CD 316 Chédiak-Higashi Syndrome LYST 317 Schimke immuno-osseous dysplasia SMARCAL1 318 Wiskott-Aldrich syndrome WAS 319 CNV X-linked agammaglobulinemia with neurologic impairment and sensorineural deafness BTK 320 Atypical SCID IL7R 321,322 Very early onset-inflammatory bowel disease (VEO-IBD) XIAP 323 Ataxia-telangiectasia ATM 324 Mendelian susceptibility to mycobacterial disease (MSMD) IFNGR1 325 Severe Combined ImmunoDeficiency (SCID) DCLRE1C 326 Williams-Beuren syndrome and Chronic Granulomatous Disease (CGD) NCF1 327 DOCK8 deficiency DOCK8 328 CTLA-4 deficiency CTLA4 329 Allelic imbalance Combined immunodeficiency (Artemis CID) DCLRE1C 330 CARD9 deficiency CARD9 31 Skewed X lyonization Wiskott-Aldrich syndrome WAS 319,[331][332][333][334][335][336][337][338] X-linked hyper-IgM CD40LG 339 Chronic Granulomatous Diseases CYBB [340][341][342] Mosaicism Germline mosaicism X-linked SCID IL2RG [343][344][345] Wiskott-Aldrich syndrome WAS 346 Several disorders…”