Table 3.

Selected Genes of Interest in the Differential Diagnosis of GATA1-Related Cytopenia

GeneDisorderMOIClinical Characteristics
Thrombocytopenia
ETV6 ETV6 thrombocytopenia & predisposition to leukemia ADMild-to-moderate thrombocytopenia w/platelet function defects; ↑ risk of hematologic malignancy
RUNX1 RUNX1 familial platelet disorder w/assoc myeloid malignancies ADMild-to-moderate thrombocytopenia w/platelet function defects; ↑ risk of hematologic malignancy
WAS Wiskott-Aldrich syndrome (See WAS-Related Disorders.)XLSmall platelets, eczema (~80%), & immunodeficiency; persons may have isolated microthrombocytopenia.
Congenital macrothrombocytopenia
GP1BA
GP1BB
GP9 		Bernard-Soulier syndrome (BSS) (OMIM 231200)ARSevere bleeding disorder w/severely defective ristocetin-induced platelet agglutination; heterozygotes may have mild disease.
GP1BA
GP1BB 		Mediterranean thrombocytopenia (OMIM 153670)ADPhenotype typically milder than BSS; dysmegakaryo-cytopoiesis 2
MYH9 MYH9-related disease ADPlatelet macrocytosis, thrombocytopenia, & neutrophil inclusions; most persons have extrahematologic manifestation(s) (e.g., hearing loss, cataract, renal defects).
NBEAL2 2Gray platelet syndrome (OMIM 139090)AR 3Pale platelets &/or absent alpha granules.
Anemia
BRCA1
BRCA2
BRIP1
ERCC4
FAAP100
FANCA
FANCB
FANCC
FANCD2
FANCE
FANCF
FANCG
FANCI
FANCL
FANCM
PALB2
RAD51
RAD51C
REV7
RFWD3
SLX4
UBE2T
XRCC2 		Fanconi anemia AR
XL
AD 4		↑ chromosome breakage; onset of cytopenias typically at early school age; short stature, café au lait macules, & characteristic limb abnormalities may be present; ↑ risk of malignancy
EFL1
DNAJC21
SBDS
SRP54 		Shwachman-Diamond syndrome AR
AD 5		Normocytic anemia & neutropenia are most common cytopenias; exocrine pancreatic dysfunction
Macrocytic anemia
RPL11
RPL15
RPL18
RPL26
RPL27
RPL31
RPL35
RPL35A
RPL5
RPL9
RPS10
RPS15A
RPS17
RPS19
RPS24
RPS26
RPS27
RPS28
RPS29
RPS7
TSR2 		Diamond-Blackfan anemia AD 7
XL 8		Pure red cell aplasia w/normocellular marrow; growth deficiency, limb abnormalities, cardiac defects, & characteristic facies may be present; ↑ risk of malignancy

AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; XL = X-linked

1.
2.

One person with gray platelet syndrome (GPS) had a GATA1 pathogenic variant (see Genetically Related Disorders).

3.

GPS can be inherited in an autosomal recessive manner (NBEAL2-related GPS); apparent autosomal dominant or X-linked transmission have been reported (reviewed in Nurden & Nurden [2007]).

4.

Fanconi anemia (FA) can be inherited in an autosomal recessive manner, an autosomal dominant manner (RAD51-related FA), or an X-linked manner (FANCB-related FA).

5.

Shwachman-Diamond syndrome (SDS) caused by pathogenic variants in DNAJC21, EFL1, or SBDS is inherited in an autosomal recessive manner. SDS caused by pathogenic variants in SRP54 is inherited in an autosomal dominant manner; most such affected individuals reported to date have a de novo SRP54 pathogenic variant.

7.

Approximately 40%-45% of individuals with autosomal dominant Diamond-Blackfan anemia (DBA) inherited the pathogenic variant from a parent; approximately 55%-60% have a de novo pathogenic variant.

8.

DBA is most often inherited in an autosomal dominant manner; TSR2-related DBA is inherited in an X-linked manner.

From: GATA1-Related Cytopenia

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