Homozygotes or compound heterozygotes
for BT who co-inherited AT have less redundant [alpha]-globin and therefore present with less severity.
HFE C282Y/H63D compound heterozygotes
are at low risk of hemochromatosis-related morbidity.
This high incidence is mostly due to the high rate of consanguineous marriages in Turkey (overall 22%, increasing to 34% in South East Anatolia region) giving rise to higher incidence of homozygous biallelic mutations in this population together with compound heterozygotes
for two or more different mutant CYP21A2 alleles (3).
H63D and S65C mutations are also commonly detected but are generally only associated with iron overload in C282Y/H63D or C282Y/S65C compound heterozygotes
(, Bacon BR).
 compared clinical information from 131 individuals with homozygous expansions and 111 compound heterozygotes
. Structural modeling and stability analyses were used to predict protein stability and protein interaction disruption of the various missense mutations.
GAA activities from individuals with pseudodeficiency alleles was summarized in 3 groups based on the combinations of the 2 alleles: homozygotes for the common pseudodeficiency allele [p.G576S_E689K] (PD/PD), compound heterozygotes
of a pseudodeficiency allele and a pathogenic allele (PD/Pathogenic), and compound heterozygotes
of a pseudodeficiency allele and a VOUS (PD/VOUS).
The proband and his affected sister were compound heterozygotes
for c.916G>A (p.Ala306Thr) and one novel mutation c.1250G>A (p.Gly417Glu).
The Hb Lepore has also been found in compound heterozygotes
for Hbs S, C, and E.
The genetic pathogenesis mainly involves three different gene alterations; they can be homozygotes, compound heterozygotes
or double heterozygotes.
Since all three patients have clear clinical and biochemical characteristics of 11[beta]-OHD, we assume that the patients are compound heterozygotes
, and that the mutations are located on different alleles.
PATHOPHYSIOLOGY OF COMPOUND HETEROZYGOTES
INVOLVING HEMOGLOBINOPATHIES AND THALASSEMIAS
Heterozygotes for C282Y, the homozygosity for variant H63D, and the compound heterozygotes
of H63D and C282Y also succumb to hemochromatosis with a lower penetrance (Burke et al.