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Jaeran Lee - One of the best experts on this subject based on the ideXlab platform.
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Autosomal Dominant transmission of complicated hereditary spastic paraplegia due to a Dominant negative mutation of KIF1A, SPG30 gene.
NATURE PUBLISHING GROUP, 2018Co-Authors: Chong Kun Cheon, Doyoun Kim, So Hee Lim, Eunjoon Kim, Yoo-mi Kim, Na-yoon Lee, Tae-sung Yoon, Nam-soon Kim, Jaeran LeeAbstract:KIF1A is a brain-specific anterograde motor protein that transports cargoes towards the plus-ends of microtubules. Many variants of the KIF1A gene have been associated with neurodegenerative diseases and developmental delay. Homozygous mutations of KIF1A have been identified in a recessive subtype of hereditary spastic paraplegia (HSP), SPG30. In addition, KIF1A mutations have been found in pure HSP with autosomal Dominant Inheritance. Here we report the first case of familial complicated HSP with a KIF1A mutation transmitted in autosomal Dominant Inheritance. A heterozygous p.T258M mutation in KIF1A was found in a Korean family through targeted exome sequencing. They displayed phenotypes of mild intellectual disability with language delay, epilepsy, optic nerve atrophy, thinning of corpus callosum, periventricular white matter lesion, and microcephaly. A structural modeling revealed that the p.T258M mutation disrupted the binding of KIF1A motor domain to microtubules and its movement along microtubules. Assays of peripheral accumulation and proximal distribution of KIF1A motor indicated that the KIF1A motor domain with p.T258M mutation has reduced motor activity and exerts a Dominant negative effect on wild-type KIF1A. These results suggest that the p.T258M mutation suppresses KIF1A motor activity and induces complicated HSP accompanying intellectual disability transmitted in autosomal Dominant Inheritance. © The Author(s) 20171
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Autosomal Dominant transmission of complicated hereditary spastic paraplegia due to a Dominant negative mutation of KIF1A, SPG30 gene.
Scientific reports, 2017Co-Authors: Chong Kun Cheon, Doyoun Kim, So Hee Lim, Eunjoon Kim, Yoo-mi Kim, Na-yoon Lee, Tae-sung Yoon, Nam-soon Kim, Jaeran LeeAbstract:KIF1A is a brain-specific anterograde motor protein that transports cargoes towards the plus-ends of microtubules. Many variants of the KIF1A gene have been associated with neurodegenerative diseases and developmental delay. Homozygous mutations of KIF1A have been identified in a recessive subtype of hereditary spastic paraplegia (HSP), SPG30. In addition, KIF1A mutations have been found in pure HSP with autosomal Dominant Inheritance. Here we report the first case of familial complicated HSP with a KIF1A mutation transmitted in autosomal Dominant Inheritance. A heterozygous p.T258M mutation in KIF1A was found in a Korean family through targeted exome sequencing. They displayed phenotypes of mild intellectual disability with language delay, epilepsy, optic nerve atrophy, thinning of corpus callosum, periventricular white matter lesion, and microcephaly. A structural modeling revealed that the p.T258M mutation disrupted the binding of KIF1A motor domain to microtubules and its movement along microtubules. Assays of peripheral accumulation and proximal distribution of KIF1A motor indicated that the KIF1A motor domain with p.T258M mutation has reduced motor activity and exerts a Dominant negative effect on wild-type KIF1A. These results suggest that the p.T258M mutation suppresses KIF1A motor activity and induces complicated HSP accompanying intellectual disability transmitted in autosomal Dominant Inheritance.
Chong Kun Cheon - One of the best experts on this subject based on the ideXlab platform.
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Autosomal Dominant transmission of complicated hereditary spastic paraplegia due to a Dominant negative mutation of KIF1A, SPG30 gene.
NATURE PUBLISHING GROUP, 2018Co-Authors: Chong Kun Cheon, Doyoun Kim, So Hee Lim, Eunjoon Kim, Yoo-mi Kim, Na-yoon Lee, Tae-sung Yoon, Nam-soon Kim, Jaeran LeeAbstract:KIF1A is a brain-specific anterograde motor protein that transports cargoes towards the plus-ends of microtubules. Many variants of the KIF1A gene have been associated with neurodegenerative diseases and developmental delay. Homozygous mutations of KIF1A have been identified in a recessive subtype of hereditary spastic paraplegia (HSP), SPG30. In addition, KIF1A mutations have been found in pure HSP with autosomal Dominant Inheritance. Here we report the first case of familial complicated HSP with a KIF1A mutation transmitted in autosomal Dominant Inheritance. A heterozygous p.T258M mutation in KIF1A was found in a Korean family through targeted exome sequencing. They displayed phenotypes of mild intellectual disability with language delay, epilepsy, optic nerve atrophy, thinning of corpus callosum, periventricular white matter lesion, and microcephaly. A structural modeling revealed that the p.T258M mutation disrupted the binding of KIF1A motor domain to microtubules and its movement along microtubules. Assays of peripheral accumulation and proximal distribution of KIF1A motor indicated that the KIF1A motor domain with p.T258M mutation has reduced motor activity and exerts a Dominant negative effect on wild-type KIF1A. These results suggest that the p.T258M mutation suppresses KIF1A motor activity and induces complicated HSP accompanying intellectual disability transmitted in autosomal Dominant Inheritance. © The Author(s) 20171
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Autosomal Dominant transmission of complicated hereditary spastic paraplegia due to a Dominant negative mutation of KIF1A, SPG30 gene.
Scientific reports, 2017Co-Authors: Chong Kun Cheon, Doyoun Kim, So Hee Lim, Eunjoon Kim, Yoo-mi Kim, Na-yoon Lee, Tae-sung Yoon, Nam-soon Kim, Jaeran LeeAbstract:KIF1A is a brain-specific anterograde motor protein that transports cargoes towards the plus-ends of microtubules. Many variants of the KIF1A gene have been associated with neurodegenerative diseases and developmental delay. Homozygous mutations of KIF1A have been identified in a recessive subtype of hereditary spastic paraplegia (HSP), SPG30. In addition, KIF1A mutations have been found in pure HSP with autosomal Dominant Inheritance. Here we report the first case of familial complicated HSP with a KIF1A mutation transmitted in autosomal Dominant Inheritance. A heterozygous p.T258M mutation in KIF1A was found in a Korean family through targeted exome sequencing. They displayed phenotypes of mild intellectual disability with language delay, epilepsy, optic nerve atrophy, thinning of corpus callosum, periventricular white matter lesion, and microcephaly. A structural modeling revealed that the p.T258M mutation disrupted the binding of KIF1A motor domain to microtubules and its movement along microtubules. Assays of peripheral accumulation and proximal distribution of KIF1A motor indicated that the KIF1A motor domain with p.T258M mutation has reduced motor activity and exerts a Dominant negative effect on wild-type KIF1A. These results suggest that the p.T258M mutation suppresses KIF1A motor activity and induces complicated HSP accompanying intellectual disability transmitted in autosomal Dominant Inheritance.
Moshe Phillip - One of the best experts on this subject based on the ideXlab platform.
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Familial central precocious puberty suggests autosomal Dominant Inheritance
2020Co-Authors: Liat De Vries, Arieh Kauschansky, Mordechai Shohat, Moshe PhillipAbstract:The prevalence of precocious puberty is higher in certain ethnic groups, and some cases may be familial. The aim of this study was to investigate the mode of Inheritance of familial precocious puberty and to identify characteristics that distinguish familial from isolated precocious puberty. Of the 453 children referred to our center for suspected precocious puberty between January 1, 1997, and December 31, 2000, 156 (147 girls and 9 boys) were found to have idiopathic central precocious puberty, which was familial in 43 (42 girls and 1 boy) (27.5%). Data of the familial and sporadic cases were compared. The familial group was characterized by a significantly lower maternal age at menarche than the sporadic group (mean, 11.47 ؎ 1.96 vs. 12.66 ؎ 1.18 yr; P ؍ 0.0001) and more advanced puberty at admission (Tanner stage 2, 56.5% vs. 78.1%; P ؍ 0.006). Segregation analysis was used to study the mode of Inheritance. The segregation ratio for precocious puberty was 0. (1) demonstrated that puberty may occur at an earlier age than previously thought, with a rate of early puberty four times higher in African-American girls than in Caucasian girls. This observation suggested a genetic regulation of the timing of puberty. Some pediatric endocrinologists believe that the pubertal pattern may be influenced by familial trends, such that families with one member with precocious puberty have a higher than normal probability of having another. However, scientific support for this assumption remains sparse. We found only a few published descriptions of cases of familial central precocious puberty (2-6) and only one study (3) of the prevalence of familial cases in a series of 58 patients with central precocious puberty. In the present study, we sought to determine the mode of Inheritance of familial precocious puberty (FPP) in families with central precocious puberty and to identify specific clinical or laboratory features that distinguish familial from sporadic cases. We also calculated the prevalence of FPP at our tertiary care center in a given period of time. Patients and Methods Patients Of the 453 children evaluated in our clinic for precocious secondary sexual development between January 1, 1997, and December 31, 2000, 156 were found to have idiopathic central precocious puberty. The rest presented with precocious adrenarche (n ϭ 101), early puberty (n ϭ 89), premature thelarche (n ϭ 58), obesity associated with pseudothelarche (n ϭ 19), and other diagnoses (n ϭ 26); four were lost to follow-up. The diagnosis of precocious puberty was based on the presence of secondary sexual characteristics before age 8 yr in females and 9 yr in males. In girls, central precocious puberty was diagnosed on the basis of clinical characteristics, including appearance of breast buds before 8 yr of age accompanied by the presence of one or more of the following findings: menses, pubic hair, accelerated growth velocity, or bone age greater than 2 sd above chronological age. When the clinical picture was not obvious, the patients were followed for at least 6 months before the diagnosis was made. Adopted girls were excluded, as were girls with chronic disease, bone dysplasia, organic brain disease, congenital adrenal hyperplasia or other endocrinological abnormalities, and girls who had received radiation therapy and/or chemotherapy. Written informed consent was obtained from all families. The study was approved by the institutional human research committee. Methods At the first visit, the pedigree was determined, detailing medical illnesses and timing of puberty in family members. The parents completed a structured questionnaire including items on puberty in first-, second-, and third-degree relatives, and they were asked to contact directly the children's grandparents, aunts, uncles, and cousins to determine the age of puberty directly from them. We collected the data by contacting the parents by phone. First-degree relatives were defined as mother, father, brother(s), and sister(s); second-degree relatives as grandparents, aunt(s), and uncle(s); and third-degree relatives as cousins. Females were asked about age at appearance of breast buds and age at menarche and males about age at onset of pubertal changes and age at initiation of full-face shaving. Those who met the following criteria were included in the study group of FPP: 1) presentation with gonadotropin-dependent central precocious puberty, as described above; and 2) at least one of the following: menarche at age 10 yr or earlier in a first-, second-, or third-degree female relative; clinically documented precocious puberty, as described above, in a first-, second-, or third-degree relative; or full puberty, including full facial shaving, earlier than age 13 yr in a first-, second-, or third-degree male relative. [For Jewish males, age 13 (bar mitzvah) is a significant and well-remembered milestone.] Girls with idiopathic central precocious puberty without a family history were considered to have sporadic precocious puberty (SPP). All patients underwent clinical, biochemical, and bone age evaluation on admission. Pubertal stage was determined according to Marshall and Abbreviations: BMI, Body mass index; FPP, familial precocious puberty; SDS, sd score; SPP, sporadic precocious puberty. JCEM is published monthly by The Endocrine Society (http://www. endo-society.org), the foremost professional society serving the endocrine community
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familial central precocious puberty suggests autosomal Dominant Inheritance
The Journal of Clinical Endocrinology and Metabolism, 2004Co-Authors: Liat De Vries, Arieh Kauschansky, Mordechai Shohat, Moshe PhillipAbstract:The prevalence of precocious puberty is higher in certain ethnic groups, and some cases may be familial. The aim of this study was to investigate the mode of Inheritance of familial precocious puberty and to identify characteristics that distinguish familial from isolated precocious puberty. Of the 453 children referred to our center for suspected precocious puberty between January 1, 1997, and December 31, 2000, 156 (147 girls and 9 boys) were found to have idiopathic central precocious puberty, which was familial in 43 (42 girls and 1 boy) (27.5%). Data of the familial and sporadic cases were compared. The familial group was characterized by a significantly lower maternal age at menarche than the sporadic group (mean, 11.47 ± 1.96 vs. 12.66 ± 1.18 yr; P = 0.0001) and more advanced puberty at admission (Tanner stage 2, 56.5% vs. 78.1%; P = 0.006). Segregation analysis was used to study the mode of Inheritance. The segregation ratio for precocious puberty was 0.38 (0.45 after exclusion of young siblings) ...
Nam-soon Kim - One of the best experts on this subject based on the ideXlab platform.
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Autosomal Dominant transmission of complicated hereditary spastic paraplegia due to a Dominant negative mutation of KIF1A, SPG30 gene.
NATURE PUBLISHING GROUP, 2018Co-Authors: Chong Kun Cheon, Doyoun Kim, So Hee Lim, Eunjoon Kim, Yoo-mi Kim, Na-yoon Lee, Tae-sung Yoon, Nam-soon Kim, Jaeran LeeAbstract:KIF1A is a brain-specific anterograde motor protein that transports cargoes towards the plus-ends of microtubules. Many variants of the KIF1A gene have been associated with neurodegenerative diseases and developmental delay. Homozygous mutations of KIF1A have been identified in a recessive subtype of hereditary spastic paraplegia (HSP), SPG30. In addition, KIF1A mutations have been found in pure HSP with autosomal Dominant Inheritance. Here we report the first case of familial complicated HSP with a KIF1A mutation transmitted in autosomal Dominant Inheritance. A heterozygous p.T258M mutation in KIF1A was found in a Korean family through targeted exome sequencing. They displayed phenotypes of mild intellectual disability with language delay, epilepsy, optic nerve atrophy, thinning of corpus callosum, periventricular white matter lesion, and microcephaly. A structural modeling revealed that the p.T258M mutation disrupted the binding of KIF1A motor domain to microtubules and its movement along microtubules. Assays of peripheral accumulation and proximal distribution of KIF1A motor indicated that the KIF1A motor domain with p.T258M mutation has reduced motor activity and exerts a Dominant negative effect on wild-type KIF1A. These results suggest that the p.T258M mutation suppresses KIF1A motor activity and induces complicated HSP accompanying intellectual disability transmitted in autosomal Dominant Inheritance. © The Author(s) 20171
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Autosomal Dominant transmission of complicated hereditary spastic paraplegia due to a Dominant negative mutation of KIF1A, SPG30 gene.
Scientific reports, 2017Co-Authors: Chong Kun Cheon, Doyoun Kim, So Hee Lim, Eunjoon Kim, Yoo-mi Kim, Na-yoon Lee, Tae-sung Yoon, Nam-soon Kim, Jaeran LeeAbstract:KIF1A is a brain-specific anterograde motor protein that transports cargoes towards the plus-ends of microtubules. Many variants of the KIF1A gene have been associated with neurodegenerative diseases and developmental delay. Homozygous mutations of KIF1A have been identified in a recessive subtype of hereditary spastic paraplegia (HSP), SPG30. In addition, KIF1A mutations have been found in pure HSP with autosomal Dominant Inheritance. Here we report the first case of familial complicated HSP with a KIF1A mutation transmitted in autosomal Dominant Inheritance. A heterozygous p.T258M mutation in KIF1A was found in a Korean family through targeted exome sequencing. They displayed phenotypes of mild intellectual disability with language delay, epilepsy, optic nerve atrophy, thinning of corpus callosum, periventricular white matter lesion, and microcephaly. A structural modeling revealed that the p.T258M mutation disrupted the binding of KIF1A motor domain to microtubules and its movement along microtubules. Assays of peripheral accumulation and proximal distribution of KIF1A motor indicated that the KIF1A motor domain with p.T258M mutation has reduced motor activity and exerts a Dominant negative effect on wild-type KIF1A. These results suggest that the p.T258M mutation suppresses KIF1A motor activity and induces complicated HSP accompanying intellectual disability transmitted in autosomal Dominant Inheritance.
So Hee Lim - One of the best experts on this subject based on the ideXlab platform.
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Autosomal Dominant transmission of complicated hereditary spastic paraplegia due to a Dominant negative mutation of KIF1A, SPG30 gene.
NATURE PUBLISHING GROUP, 2018Co-Authors: Chong Kun Cheon, Doyoun Kim, So Hee Lim, Eunjoon Kim, Yoo-mi Kim, Na-yoon Lee, Tae-sung Yoon, Nam-soon Kim, Jaeran LeeAbstract:KIF1A is a brain-specific anterograde motor protein that transports cargoes towards the plus-ends of microtubules. Many variants of the KIF1A gene have been associated with neurodegenerative diseases and developmental delay. Homozygous mutations of KIF1A have been identified in a recessive subtype of hereditary spastic paraplegia (HSP), SPG30. In addition, KIF1A mutations have been found in pure HSP with autosomal Dominant Inheritance. Here we report the first case of familial complicated HSP with a KIF1A mutation transmitted in autosomal Dominant Inheritance. A heterozygous p.T258M mutation in KIF1A was found in a Korean family through targeted exome sequencing. They displayed phenotypes of mild intellectual disability with language delay, epilepsy, optic nerve atrophy, thinning of corpus callosum, periventricular white matter lesion, and microcephaly. A structural modeling revealed that the p.T258M mutation disrupted the binding of KIF1A motor domain to microtubules and its movement along microtubules. Assays of peripheral accumulation and proximal distribution of KIF1A motor indicated that the KIF1A motor domain with p.T258M mutation has reduced motor activity and exerts a Dominant negative effect on wild-type KIF1A. These results suggest that the p.T258M mutation suppresses KIF1A motor activity and induces complicated HSP accompanying intellectual disability transmitted in autosomal Dominant Inheritance. © The Author(s) 20171
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Autosomal Dominant transmission of complicated hereditary spastic paraplegia due to a Dominant negative mutation of KIF1A, SPG30 gene.
Scientific reports, 2017Co-Authors: Chong Kun Cheon, Doyoun Kim, So Hee Lim, Eunjoon Kim, Yoo-mi Kim, Na-yoon Lee, Tae-sung Yoon, Nam-soon Kim, Jaeran LeeAbstract:KIF1A is a brain-specific anterograde motor protein that transports cargoes towards the plus-ends of microtubules. Many variants of the KIF1A gene have been associated with neurodegenerative diseases and developmental delay. Homozygous mutations of KIF1A have been identified in a recessive subtype of hereditary spastic paraplegia (HSP), SPG30. In addition, KIF1A mutations have been found in pure HSP with autosomal Dominant Inheritance. Here we report the first case of familial complicated HSP with a KIF1A mutation transmitted in autosomal Dominant Inheritance. A heterozygous p.T258M mutation in KIF1A was found in a Korean family through targeted exome sequencing. They displayed phenotypes of mild intellectual disability with language delay, epilepsy, optic nerve atrophy, thinning of corpus callosum, periventricular white matter lesion, and microcephaly. A structural modeling revealed that the p.T258M mutation disrupted the binding of KIF1A motor domain to microtubules and its movement along microtubules. Assays of peripheral accumulation and proximal distribution of KIF1A motor indicated that the KIF1A motor domain with p.T258M mutation has reduced motor activity and exerts a Dominant negative effect on wild-type KIF1A. These results suggest that the p.T258M mutation suppresses KIF1A motor activity and induces complicated HSP accompanying intellectual disability transmitted in autosomal Dominant Inheritance.