Table.

FHL1 mutations and clinical characteristics in X-linked myopathy

Residuea	LIM	Zincb	Inheritc/sex	Onset age	Wheelchair-bound aged	Phenotype/Affected Musclese	CK	Femalesf	Pathologyg	W. Bloth	Ref.
C101F	2nd	Zn1	SF	2	died at 3	proximal muscles respiratory failure	↑	asymp.	RB, RV, AV, pyknotic Nu. IC. of FHL1, α5-integrin, MyHC	↓	[5]
102–104 delKFC	2nd	Zn1	SF	40s	NA	distal muscles	NA	asymp.	RB, RV, IC. of FHL1, α5-integrin, MyHC	↑	[5]
C104R	2nd	Zn1	XLD	10	no, current 11	scapuloperoneal Gowers’, rigid spine	↑	o.29 wcb.34	RB IC. of FHL1, α5-integrin, MyHC	↓	[5]
111–229 delG-T	2nd–4th	Zn1, 2	XLR	14	no, current 35	scapuloperoneal joints contractures RBBB, respiratory failure	↑ ↑	asymp.	non specific myopathic changes	NA	[7]
W122C*	2nd	NBS	XLD	30s	40s–50s	scapuloperoneal hypertrophy respiratory insufficiency	↑	o.73, mild	RV, necrotic, atrophic fibers, IC. of FHL1, desmin, Ub	NA	This report
W122S*	2nd	NBS	XLD	20s	30s	scapuloperoneal hypertrophy respiratory failure	↑	o.30s wcb.50s	NA	↓	[2]
H123Y*	2nd	Zn1	SF	<2	3	proximal muscle rigid spine respiratory failure	↑	asymp.	RB, IC. of FHL1, desmin, Ub	nl	[1]
H123Y	2nd	Zn1	SF	<1.5	no, current 2.5	proximal muscle, neck Gowers’	mild ↑	asymp.	RB, RV, IC. of FHL1, pericentrin, tubulin	NA	[6]
H123L	2nd	Zn1	SF	4	no, current 7	generalized hypotrophy scapular Gowers’, scoliosis	nl.	asymp.	RB, RV, IC. of FHL1, pericentrin, tubulin	NA	[6]
H123Q*	2nd	Zn1	SF	4	10	proximal and axial scapular, scoliosis	↑	asymp.	RB, RV, IC. of FHL1, pericentrin, tubulin	NA	[6]
H123Q	2nd	Zn1	SF	3	8	neck, axial Gowers’, scoliosis respiratory insufficiency	↑ ↑	asymp.	RB, RV, IC. of FHL1, pericentrin, tubulin	NA	[6]
H123Q	2nd	Zn1	SM	1	2	proximal, scoliosis cardiomyopathy, respiratory insufficiency	↑ ↑	asymp.	RB, RV, IC. of FHL1, pericentrin, tubulin	NA	[6]
K124Rfs X6	2nd	Zn1, 2	XLD	10	no, current 26	humeral, peroneal, facial JC, RBBB, AFb	↑	NA	dystrophic	↓	[7]
127–128in sFT	2nd	NBS	XLR	30s–40s	50s	postural, hypertrophy respiratory failure	↑ ↑	asymp.	Atrophy and necrotic fibers. Variation in fiber size	NA	[3]
C132F*	2nd	Zn1	SF	2	4.5, died at 6.5	generalized hypotrophy respiratory failure	↑	asymp.	RB, IC. of FHL1, desmin, Ub	↑	[1]
C150Y*	2nd	Zn2	SF	2.5	died at 4.5	proximal muscles respiratory failure	mild ↑	asymp.	RB, RV, AV, pyknotic Nu.	NA	[5]
151–153 delVTC	2nd	Zn2	SM?	13	no, current 16	scapuloperoneal, rigid spine, Gowers’	mild ↑	asymp.	RB, RV, increased FHL1staining	↓	[4]
C153R	2nd	Zn2	XLD	5	8	proximal, cardiomyopathy respiratory insufficiency	↑ ↑	o.30s wcb.40s	RB	NA	[1]
C153Y	2nd	Zn2	XLD	10	16	proximal muscles rigid spine	↑	o.30s	RB	NA	[1]
K157Vfs X36	2nd	Zn1, 2	XLD	4	no, current 23	scapuloperoneal, facial, JC, heart hypertrophy	↑	cardiac disease	non specific myopathic changes	↓	[7]
A168Gfs X27	2nd	Zn1, 2	XLD	20s	NA	rigid spine, sinus valsalvae aneurysm	↑ ↑	o. 50s	protein body, loss of FHL1 staining	absent	[8]
C209R	3rd	Zn2	XLD	11	no, current 41	scapular, pelvic, JC arrhythmias	↑ ↑	o.10to69	dystrophic changes	↓	[7]
C224W	4th	Zn1	XLR	30s	died at 45–72	postural, scapulo-axio-peroneal, hypertrophy cardiomyopathy respiratory failure	↑ or ↑ ↑	asymp.	core-like in NADH, AV FHL1 absent or reduced staining	absent	[3]
C224W	4th	Zn1	XLR/XLD	6–45	NA	rigid spine, hypertrophy scapuloperoneal respiratory failure	↑	asymp.	absent FHL1 staining	absent	[8]
H246Y	4th	Zn1	SM?	17	NA	rigid spine, scapuloperoneal	mild ↑	asymp.	hypertrophy, FHL1 no staining	NA	[8]
C273Lfs X11	4th	Zn2	XLD	6	no, current 30	scapular, pelvic hypertrophy, JC	↑	cardiac disease	non specific myopathic changes	NA	[7]
C276Y	4th	Zn2	XLR	48	no, current 54	axial, pelvic, hypertrophy JC, AFb, AFI	↑	asymp	dystrophic/myopathic reduced FHL1 staining	↓	[7]
V280M	4th	NBS	XLR	8	NA	rigid spine, scapuloperoneal	↑	asymp	absent FHL1 staining	absent	[8]
X281E	4th	NBS	XLR	10	no, current 18	Scapuloperoneal, JC septal hypertrophy	↑	asymp	dystrophic reduced FHL1 staining	↓	[7]

Notes:

^a* = mutations studied in molecular dynamics simulations; ins = in-frame nucleotide insertion; del = in-frame nucleotide deletion; fsX = frameshifting mutation, with the following number indicating the number of new amino acids downstream of the mutation preceding introduction of a premature stop codon.

^bBinding to the first or second Zn of the domain; NBS = not a binding site.

^cInheritance pattern: SF = sporadic female; SM = sporadic male; XLD = X-linked dominant; XLR = X-linked recessive.

^dAge (years) at which patient became wheel-chair bound or died, or current age if still ambulatory; NA=not available

^eJC = joint contractures; RBBB = right bundle branch block; AFb = atrial fibrillation; AFI = atrial flutter

^fMyopathy symptoms in female members: o = age of onset; wcb = age at which wheelchair bound; asymp = asymptomatic.

^gRB = reducing bodies; RV = rimmed vacuoles; AV = autophagy vacuoles; Nu = nucleus; IC = inclusion; Ub = ubiquitin;

^hFHL1 expression level by western blot; nl = normal.