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Kalsi, et al.

(2003) using single-stranded conformational polymorphism

(SSCP) investigated impact of NM_000036.2:c.133C>T p.Gln45Ter (in this
article referred to as C34T, Glu12Stop, Q12X) mutation of AMPD1 gene on
AMP-deaminase enzyme activity in cardiac muscle, as well as in
systematic changes of adenosine serum concentration in 27 test subjects
with heart failure (HF) (22 male, 5 female, 41.32.8 years of age) and in
21 Caucasian unaffected controls (age range14-35) with established
AMPD1 genotype after exhaustive exercise and at rest. AMP-deaminase
enzyme activity was lower in individuals with heterozygous (C/T)
NM_000036.2:c.133C>T (p.Gln45Ter) mutation (n=8), versus wild type (C/C)
control patients
(n=19), p=0.003. Blood adenosine concentration
remained unchanged 4min after 1min maximum exercise in controls with
wild type (C/C n=10) and in group of heterozygous individuals (C/T n=6),
NM_000036.2:c.133C>T (p.Gln45Ter) individuals (T/T n=5); p=0.035.
Adding to the previously demonstrated cardio-protective capacity of this
mutation, the authors conclude that NM_000036.2:c.133C>T (p.Gln45Ter)
mutation causes a decrease in the activity of AMP-deaminase locally in
cardiac muscle which they postulate confers improved survival in patients
with heart disease, as the systemic change in adenosine concentration
was relatively small and thus unlikely to play a major cardio-protective role
PMID: 14499869
Morisaki, et al. (1992) in their study aimed to define role of AMPD1gene
mutationin energy metabolim using direct sequencing of PCR products in
11 unrelated individuals (4 female, 7 male, 16-68 years of age) with
myophaty and with reduced level of AMPD activity and in a group of
normal volunteers (59 Caucasians, 13 African Americans and 106
Japanese) without knowledge of the medical history. . Presense of
homozygous (T/T); NM_000036.2:c.133C>T (p.Gln45Ter) (in this article
referred to as C34T) mutation was identified in all 11 probands with
myophaty with significantly decreased AMPD enzyme activity. In the
control group , NM_000036.2:c.133C>T (p.Gln45Ter) mutation was found
in 23% African Americans, 17% Caucasians; where two Caucasians and
one of African-Americans were found to be homozygous for this mutation,
whereas none of 106 Japanese harbored this mutation/. Since ~20% of
Caucasians and African Americans harbor the heterozygous mutation, and
1-3% of random muscle biopsy samples show AMPD deficiency, but not
express clinical symptoms of metabolic myophaty, authors question the
clinical significance of this mutation and offer several theories that require
further investigation (mutation compensation through alternative splicing,
AMPD activity encoded by other members of the multigene family,
possible symptom development only in individuals with other inherited
metabolic abnormalities). PMID: 1631143
Castro-Gago, et al. (2011) reported a 6 months old Spanish female
infant with proven homozygous NM_000036.2:c.133C>T (p.Gln45Ter) (in
this article refereed as C34T, Q12X) mutation of AMPD1 gene using PCR,
RFLP and direct sequencing, that led to loss of AMPD1 enzyme activity
which was manifested with congenital muscle weakness and hypotonia of

trunk and upper limbs. She also had macrocephaly, however ocular
movements were normal. Brain MRI and motor nerve conduction velocity
were normal. Babys mother was heterozygous for this mutation, without
any clinical manifestation of the disease. Authors conclude that
manifestation of congenital weakness and hypotonia might be connected
to potential existence of primary adenosine monophosphate deaminase
deficiency, suggesting histochemical /molecular analysis to be performed
in each adenosine monophospate deaminase negative case .- PMID: 21343608