DOCK8 Deficiency Presenting as an IPEX-Like Disorder
被引:37
|
作者:
Alroqi, Fayhan J.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Med Sch, Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Room 10-214,1 Blackfan St, Boston, MA 02115 USA
King Saud bin Abdulaziz Univ Hlth Sci, King Abdulaziz Med City, Dept Pediat, Riyadh, Saudi ArabiaHarvard Med Sch, Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Room 10-214,1 Blackfan St, Boston, MA 02115 USA
Alroqi, Fayhan J.
[1
,2
]
Charbonnier, Louis-Marie
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Med Sch, Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Room 10-214,1 Blackfan St, Boston, MA 02115 USAHarvard Med Sch, Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Room 10-214,1 Blackfan St, Boston, MA 02115 USA
Charbonnier, Louis-Marie
[1
]
Keles, Sevgi
论文数: 0引用数: 0
h-index: 0
机构:
Necmettin Erbakan Univ, Div Pediat Allergy & Immunol, Konya, TurkeyHarvard Med Sch, Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Room 10-214,1 Blackfan St, Boston, MA 02115 USA
Keles, Sevgi
[3
]
Ghandour, Fatima
论文数: 0引用数: 0
h-index: 0
机构:
St George Hosp Univ, Dept Pathol, Med Ctr, Beirut, LebanonHarvard Med Sch, Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Room 10-214,1 Blackfan St, Boston, MA 02115 USA
Ghandour, Fatima
[4
]
Mouawad, Pierre
论文数: 0引用数: 0
h-index: 0
机构:
St George Hosp Univ, Dept Pediat, Med Ctr, Beirut, LebanonHarvard Med Sch, Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Room 10-214,1 Blackfan St, Boston, MA 02115 USA
Mouawad, Pierre
[5
]
Sabouneh, Rami
论文数: 0引用数: 0
h-index: 0
机构:
St George Hosp Univ, Dept Pediat, Med Ctr, Beirut, LebanonHarvard Med Sch, Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Room 10-214,1 Blackfan St, Boston, MA 02115 USA
Sabouneh, Rami
[5
]
Mohammed, Reem
论文数: 0引用数: 0
h-index: 0
机构:
King Saud bin Abdulaziz Univ Hlth Sci, King Abdulaziz Med City, Dept Pediat, Riyadh, Saudi ArabiaHarvard Med Sch, Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Room 10-214,1 Blackfan St, Boston, MA 02115 USA
Mohammed, Reem
[2
]
Almutairi, Abduarahman
论文数: 0引用数: 0
h-index: 0
机构:
King Saud bin Abdulaziz Univ Hlth Sci, King Abdulaziz Med City, Dept Pediat, Riyadh, Saudi ArabiaHarvard Med Sch, Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Room 10-214,1 Blackfan St, Boston, MA 02115 USA
Almutairi, Abduarahman
[2
]
Chou, Janet
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Med Sch, Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Room 10-214,1 Blackfan St, Boston, MA 02115 USAHarvard Med Sch, Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Room 10-214,1 Blackfan St, Boston, MA 02115 USA
Chou, Janet
[1
]
Massaad, Michel J.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Med Sch, Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Room 10-214,1 Blackfan St, Boston, MA 02115 USAHarvard Med Sch, Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Room 10-214,1 Blackfan St, Boston, MA 02115 USA
Massaad, Michel J.
[1
]
Geha, Raif S.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Med Sch, Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Room 10-214,1 Blackfan St, Boston, MA 02115 USAHarvard Med Sch, Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Room 10-214,1 Blackfan St, Boston, MA 02115 USA
Geha, Raif S.
[1
]
Baz, Zeina
论文数: 0引用数: 0
h-index: 0
机构:
St George Hosp Univ, Dept Pediat, Med Ctr, Beirut, LebanonHarvard Med Sch, Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Room 10-214,1 Blackfan St, Boston, MA 02115 USA
Baz, Zeina
[5
]
Chatila, Talal A.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Med Sch, Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Room 10-214,1 Blackfan St, Boston, MA 02115 USAHarvard Med Sch, Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Room 10-214,1 Blackfan St, Boston, MA 02115 USA
Chatila, Talal A.
[1
]
机构:
[1] Harvard Med Sch, Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Room 10-214,1 Blackfan St, Boston, MA 02115 USA
[2] King Saud bin Abdulaziz Univ Hlth Sci, King Abdulaziz Med City, Dept Pediat, Riyadh, Saudi Arabia
The dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive-combined immunodeficiency whose clinical spectra include recurrent infections, autoimmunity, malignancies, elevated serum IgE, eczema, and food allergies. Here, we report on patients with loss of function DOCK8 mutations with profound immune dysregulation suggestive of an immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX)-like disorder. Immunophenotyping of lymphocyte subpopulations and analysis of DOCK8 protein expression were evaluated by flow cytometry. T regulatory (T-reg) cells were isolated by cell sorting, and their suppressive activity was analyzed by flow cytometry. Gene mutational analysis was performed by whole-exome and Sanger sequencing. Patient 1 (P1) presented at 10 months of age with chronic severe diarrhea and active colitis in the absence of an infectious trigger, severe eczema with elevated serum IgE, and autoimmune hemolytic anemia, suggestive of an IPEX-related disorder. Whole-exome sequencing revealed a homozygous nonsense mutation in DOCK8 at the DOCK-homology region (DHR)-1 (c.1498C > T; p. R500X). Patient P2, a cousin of P1 who carries the same DOCK8 nonsense mutation, presented with eczema and recurrent ear infections in early infancy, and she developed persistent diarrhea by 3 years of age. Patient P3 presented with lymphoproliferation, severe eczema with allergic dysregulation, and chronic diarrhea with colitis. She harbored a homozygous loss of function DOCK8 mutation (c.2402 -1G -> A). T-reg cell function was severely compromised by both DOCK8 mutations. DOCK8 deficiency may present severe immune dysregulation with features that may overlap with those of IPEX and other IPEX-like disorders.