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Diagnostic Gene Test Developed for Classic FOP

The single recurrent mutation in the ACVR1 gene in
patients with classic FOP is particularly amenable to
clinical genetic testing.

In 2007, a reliable diagnostic genetic test for FOP was developed
and used to diagnose FOP in seven children who were
suspected of having FOP on the basis of malformed great toes,
but prior to the onset of heterotopic ossification.
Genetic testing thus provides a level of molecular certainty
at an early stage in the disease process that can be used to
prevent unnecessary harm.

Gabrielle Haug, Shengliang Zhang and Deyu Zhang in the FOP Lab

Novel Mutations in
FOP Gene Identified in
Rare FOP Variants

Erez Lieberman, who studies the evolutionary dynamics
of language at Harvard University said, "Every rule is the tombstone
of a thousand exceptions."

Last year, we found twelve exceptions.

In 2007, we performed extensive genetic analysis on
patients with classic FOP (malformations of the great
toes and progressive heterotopic ossification), patients
with atypical FOP (those with classic features who
additionally have physical findings not commonly associated
with FOP), and those with FOP variants (those with
major variations in the classic defining features of FOP).

While all patients with classic FOP and most with atypical
FOP have the same FOP mutation, we have identified twelve
people with FOP variants who have different mutations in the FOP gene.

In some cases, there was a correlation between the location
of the mutation on the ACVR1 gene and the physical features
of the patient (especially the severity of the toe malformations),
illustrating that small gene variations can give rise to large
variations in clinical features.

Identification of disease-causing mutations in the FOP
gene has important diagnostic and therapeutic implications for
patients with all forms of FOP.

Although FOP is one of the rarest and most disabling conditions
known to mankind, its importance to clinical medicine far exceeds
the paucity of affected individuals. The FOP variants provide
extraordinary insight into the embryonic and postnatal effects
of altered ACVR1 function and dysregulated BMP signaling.
Presently, we are targeting the development of treatments to
cover all patients with classic FOP, atypical FOP, or FOP variants.