• Journal of Life Science
• /
• v.31 no.10
• /
• pp.913-921
• /
• 2021

Limb-girdle muscular dystrophy (LGMD) which is characterized by progressive muscle weakening of the hip and shoulder shows both dominant and recessive inheritances with many pathogenic genes including TTN. This study performed to identify genetic causes of a male patient with late onset (45 years old) autosomal recessive LGMD and atrial flutter. By application of the whole exome sequencing, we identified bi-allelic variants of TTN gene in the patient. One allele had a single missense variant of [c.24124G>T (p.V8042F)], while the other allele consisted of three missense variants of [c.29222G>C (p.R9741P) + c.67490A>G (p.H22497R) + c.75376C>T (p.R25126C)]. The p.V8042F allele was transmitted from his mother, while the other haplotype allele was putatively transmitted from his father. His two unaffected sons had only the p.R9741P. These variants have been not reported or rarely reported in the public human genome databases (1,000 Genome, gnomAD, and KRGDB). Most variants were located in the highly conserved immunoglobulin or fibronectin domains and were predicted to be pathogenic by the in silico analyses. The TTN giant protein plays a key role in muscle assembly, force transmission at the Z-line, and maintenance of resting tension in the I-band. In conclusion, we think that these bi-allelic compound heterozygous mutations may play a role as the genetic causes of the LGMD phenotype.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
• /
• v.8 no.1
• /
• pp.92-100
• /
• 1997

Objective：The objective of this study is to examine the clinical characteristics and behavioral comorbidity of patients with Tourette’s disorder. Method：Subjects consisted of 157 patients with Tourette’ disorder diagnosed by DSM-IIIR, who were examined and diagnosed from Jan. 1988 to May 1994 at the Tourette’s Clinic of Yonsei University Medical Center. Characteristics and behavioral comorbidity of Patients were assessed by a semi-structured interview schedule. Behavioral problems like hyperactivity, obsession-compulsion, self destructiveness, enuresis, sleep problem were assessed by global clinical impression. Results：The mean age of patients was 14.49(${\pm}7.99$) years. Patients consisted of 138 males (87.9%) and 19 females(12.1%). The sex ratio was 7：1, showing a male preponderance. The number of right-handers was 133(84.7%), and the number of non-right handers was 24(15.3%). Mean age of onset was 8.85(${\pm}4.56$) years, ranging from 2-to-16 years. More than half of the patients had their age of onset at 6-10 years. Bimodal peak in age of onset was observed；the first peak was around 6 and the second peak was around 10 years. There was no sex difference in bimodal age of onset. The most common initial symptom was eye blinking. More than 55% of patients reported eye blinking as their first symptom. The second common initial symptom was head turning and the third was vocal tic. The most common symptoms that patients reported on their first visit since onset were eye blinking(82.2%), head turning or nodding(57.9%), shoulder shrugging(52.7%) and forearm movement(32.6%). Of 157 cases, 101(64.3%) patients showed downward progression of symptoms, and 25(15.9%) showed upward progression of symptoms. Nineteen fathers(12%) of patients had a past history of obsessive-compulsive disorder(OCD). Seventeen fathers(10.6%) had a history of tic disorder. SSevenmothers(4.5%) had OCD, 4 mothers (2.5%) had tic disorder. One hundred and eighteen patients(75.1%) had comorbid hyperactivity, 95 patients(60.5%) had obsession, 55 patiens(35.0%) had self destructiveness, 46 patients(29.3%) had impulsivity, and 35 patients(22.3%) had enuresis. Age of onset had a significant positive correlation with age, duration, and the global severity of obsession；and a negative correlation with the severity of hyperactivity. Hyperactivity had a significant positive correlation with impulsivity, obsession-compulsion, enuresis, and self destructiveness. Obsession-compulsion had a significant positive correlation with hyperactivity, sleep problems, and self destructiveness. Conclusion：These data suggest that clinical characteristcs and behavioral comorbidity of patients with Tourette’ disorder in this study are similar to previous research findings in Korea and other contries. The younger the age of onset was, the more severe hyperactivity was, and the less severe obsession-compulsion was. And severity of hyperactivity had a positive correlation with the severity of obsession-compulsion, impulsivity, enuresis, and self destructiveness.