4 research outputs found
Exome sequencing identifies titin mutations causing hereditary myopathy with early respiratory failure (HMERF) in families of diverse ethnic origins
Background: Hereditary myopathy with early respiratory failure (HMERF) was described in several North European families and recently linked to a titin gene (TTN) mutation. We independently studied HMERF-like diseases with the purpose to identify the cause, refine diagnostic criteria, and estimate the frequency of this disease among myopathy patients of various ethnic origins. Methods: Whole exome sequencing analysis was carried out in a large U. S. family that included seven members suffering from skeletal muscle weakness and respiratory failure. Subsequent mutation screening was performed in further 45 unrelated probands with similar phenotypes. Studies included muscle strength evaluation, nerve conduction studies and concentric needle EMG, respiratory function test, cardiologic examination, and muscle biopsy. Results: A novel TTN p.Gly30150Asp mutation was identified in the highly conserved A-band of titin that co-segregated with the disease in the U. S. family. Screening of 45 probands initially diagnosed as myofibrillar myopathy (MFM) but excluded based on molecular screening for the known MFM genes led to the identification of a previously reported TTN p.Cys30071Arg mutation in one patient. This same mutation was also identified in a patient with suspected HMERF. The p.Gly30150Asp and p.Cys30071Arg mutations are localized to a side chain of fibronectin type III element A150 of the 10th C-zone super-repeat of titin. Conclusions: Missense mutations in TTN are the cause of HMERF in families of diverse origins. A comparison of phenotypic features of HMERF caused by the three known TTN mutations in various populations allowed to emphasize distinct clinical/pathological features that can serve as the basis for diagnosis. The newly identified p.Gly30150Asp and the p.Cys30071Arg mutation are localized to a side chain of fibronectin type III element A150 of the 10th C-zone super-repeat of titin
Serologic markers of hepatitis - B infection in bronchial asthma
Subjected to frequent parenteral drug and allergen administration, patients with bronchial asthma are likely to be at risk of contracting hepatitis B infection. In addition, those receiving immunotherapy are subjected to more frequent parenteral medication and hence are at a greater risk than those on only pharmacologic therapy.
This problem was studied among 60 patients with bronchial asthma – 30 on immunotherapy and 30 on pharmacotherapy. A higher prevalence of Hepatitis B surface antigen (HBs Ag) among patients with bronchial asthma than in the general population was detected but no difference was found between the two groups
Exome sequencing identifies titin mutations causing hereditary myopathy with early respiratory failure (HMERF) in families of diverse ethnic origins
Background: Hereditary myopathy with early respiratory failure (HMERF)
was described in several North European families and recently linked to
a titin gene (TTN) mutation. We independently studied HMERF-like
diseases with the purpose to identify the cause, refine diagnostic
criteria, and estimate the frequency of this disease among myopathy
patients of various ethnic origins.
Methods: Whole exome sequencing analysis was carried out in a large U.
S. family that included seven members suffering from skeletal muscle
weakness and respiratory failure. Subsequent mutation screening was
performed in further 45 unrelated probands with similar phenotypes.
Studies included muscle strength evaluation, nerve conduction studies
and concentric needle EMG, respiratory function test, cardiologic
examination, and muscle biopsy.
Results: A novel TTN p.Gly30150Asp mutation was identified in the highly
conserved A-band of titin that co-segregated with the disease in the U.
S. family. Screening of 45 probands initially diagnosed as myofibrillar
myopathy (MFM) but excluded based on molecular screening for the known
MFM genes led to the identification of a previously reported TTN
p.Cys30071Arg mutation in one patient. This same mutation was also
identified in a patient with suspected HMERF. The p.Gly30150Asp and
p.Cys30071Arg mutations are localized to a side chain of fibronectin
type III element A150 of the 10th C-zone super-repeat of titin.
Conclusions: Missense mutations in TTN are the cause of HMERF in
families of diverse origins. A comparison of phenotypic features of
HMERF caused by the three known TTN mutations in various populations
allowed to emphasize distinct clinical/pathological features that can
serve as the basis for diagnosis. The newly identified p.Gly30150Asp and
the p.Cys30071Arg mutation are localized to a side chain of fibronectin
type III element A150 of the 10th C-zone super-repeat of titin