(see in OMIN database for more details)
0001 MYOTUBULAR MYOPATHY,
X-LINKED [MTM1, ASN207SER]
In a male with X-linked myotubular myopathy, Laporte et al. (1996) demonstrated
an A-to-G transition of nucleotide 620 predicting a substitution of serine for
asparagine-207 in the MTM1 gene. This was 1 of 4 missense mutations that, together
with 3 frameshift mutations, were found in 7 out of 60 MTM1 patients studied.
.0002 MYOTUBULAR MYOPATHY, X-LINKED [MTM1, TYR415CYS]
In an affected individual thought to have a form of myotubular myopathy distinct
from the Xq28 form (Samson et al.,1995), Guiraud-Chaumeil et al. (1997) found
a single basepair change, 1244A-G, resulting in a change of tyrosine-415 to
cysteine in the predicted protein (called myotubularin by them). This tyrosine
coded in exon c (Laporte et al., 1996) is close to the putative tyrosine phosphatase
active site (positions 389 to 402) and is conserved in the homologs of myotubularin
in both yeast and C. elegans.
.0003 MYOTUBULAR MYOPATHY, X-LINKED [MTM1, ARG69CYS ]
In 3 patients with myotubular myopathy studied by de Gouyon et al. (1997) and
in 1 patient studied by Laporte et al. (1997), a C-to-T transition of nucleotide
259 in the MTM1 gene was identified, predicted to result in an arg69-to-cys
(R69C) amino acid substitution. The patient of Laporte et al. (1997) was still
alive at 3 years of age; 2 of the patients reported by de Gouyon et al. (1997)
were known to have had a mild phenotype and 1 of them had an affected uncle.
This mutation was associated with a CpG dinucleotide.
.0004 MYOTUBULAR MYOPATHY, X-LINKED [MTM1, IVS8, G-A, -1 ]
In a family with myotubular myopathy, Tanner et al. (1998) identified a G-to-A
transition in the acceptor splice site of intron 8 (at nucleotide 733-1).
.0005 MYOTUBULAR MYOPATHY, X-LINKED [MTM1, 4-BP DEL, NT195]
In a family with MTM1, Tanner et al. (1998) identified a 4-bp deletion (195delAGAA)
leading to a frameshift at amino acid position 66. The mutation was expected
to result in a premature stop codon and truncation of the MTM1 gene product.
.0006 MYOTUBULAR MYOPATHY, X-LINKED [MTM1, IVS11, A-G, -10 ]
In a family with X-linked myotubular myopathy, Tanner et al. (1998) found that
an A-to-G transition in intron 11 (nucleotide 1315-10) cosegregated with the
haplotype associated with the MTM1 phenotype. It was presumed that a cryptic
splice site existed at nucleotide position 1315-10. RT-PCR of muscle derived
RNA from the patient and subsequent sequencing of the obtained products proved
that splicing occurred at the new splice site. This predicted the insertion
of 3 amino acids (FIQ) in frame between exon c and exon 12 in a conserved region
of the protein.
In the tabulation of Laporte et al. (2000), this was the most frequent mutation
found in the MTM1 gene in cases of X-linked myotubular myopathy and causes a
severe myopathy.
.0007 MYOTUBULAR MYOPATHY, X-LINKED [MTM1, ARG241CYS ]
In the tabulation of Laporte et al. (2000), the second most frequent recurrent
mutation in the MTM1 gene in X-linked myotubular myopathy was a C-to-T transition
at nucleotide 721, resulting in an arg241-to-cys amino acid substitution. The
phenotype was mild in 5 patients (with 3 patients still alive at age 4 years)
and severe in 2 patients.
.0008 MYOTUBULAR MYOPATHY, X-LINKED [MTM1, ARG224TER]
Sutton et al. (2001) described a family in which the index male was hemizygous
for an arg224-to-ter (R224X) mutation in exon 8 of the MTM1 gene. The mother
and maternal grandmother were obligate carriers according to linkage analysis,
but neither showed any clinical manifestations of a myopathy. On the other hand,
a maternal aunt had noted difficulty climbing stairs at the age of 5 years followed
by progressive wasting and weakness of proximal limb muscles. Facial weakness
beginning at the age of 8 years resulted in mild dysarthria. At the age of 13
years she was noted to have scoliosis. Examination at the age of 29 years showed
bilateral facial weakness, proximal limb-girdle wasting and weakness, and bilateral
weakness of the tibialis anterior. There was no weakness of extraocular movements.
Creatine kinase was elevated at 203 IU/L. Although a skewed pattern of X-chromosome
inactivation was suspected, such was detected in either the lymphocyte or muscle
DNA of the woman, who was found to be heterozygous for the R224X mutation.
.0001 CHARCOT-MARIE-TOOTH DISEASE, TYPE 4B [MTMR2,
GLN426TER]
In an inbred Italian family with type 4B Charcot-Marie-Tooth disease (601382),
Bolino et al. (2000) identified a C-to-T transition at nucleotide 1276, resulting
in a glutamine-to-stop substitution at codon 426 (Q426X) in exon 11 of the MTMR2
gene.
.0002 CHARCOT-MARIE-TOOTH DISEASE, TYPE 4B [MTMR2, IVS13, G-A, +1]
In an inbred Saudi Arabian family with type 4B Charcot-Marie-Tooth disease (601382),
Bolino et al. (2000) found homozygosity for 2 mutations on the same allele.
One mutation was a G-to-A substitution at intron 13 at the +1 site, resulting
in in-frame exon skipping with deletion of codons 494 to 531 (1480-1593del,
phe494-glu531del). The other mutation, a G-to-T transversion at nucleotide 826,
resulted in a glutamic acid-to-stop substitution at codon 276.
.0003 CHARCOT-MARIE-TOOTH DISEASE, TYPE 4B [MTMR2, GLU276TER ]
See 603557.0002 and Bolino et al. (2000).
.0004 CHARCOT-MARIE-TOOTH DISEASE, TYPE 4B [MTMR2, GLN482TER ]
In 2 Italian sibs with Charcot-Marie-Tooth disease type 4B (601382), Bolino
et al. (2000) identified a homozygous C-to-T transition at nucleotide 1444,
resulting in a glutamine-to-termination mutation at codon 482 of the MTMR2 gene.
.0005 CHARCOT-MARIE-TOOTH DISEASE, TYPE 4B [MTMR2, 10-BP DEL/2-BP INS]
In an inbred Saudi Arabian family with Charcot-Marie-Tooth disease type 4B (601382),
Bolino et al. (2000) identified a complex mutation in exon 14, a deletion of
nucleotides 1736 to 1745 and insertion of 2 bp (CC), referred to as 1736-1745delinsCC,
leading to frameshift at tyr579 (tyr579fs) and premature translation termination.
The mutation was found in homozygosity in all affected members of the pedigree.