The Experts below are selected from a list of 1455 Experts worldwide ranked by ideXlab platform
Periasamy Sundaresan - One of the best experts on this subject based on the ideXlab platform.
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pax6 missense mutations associated in patients with optic Nerve Malformation
Molecular Vision, 2006Co-Authors: Jeyabalan Nallathambi, Guruswamy Neethirajan, Shetty Shashikant, P Vijayalakshmi, Periasamy SundaresanAbstract:Purpose: PAX6 missense mutations are likely to cause a spectrum of ocular, neurological, and systemic developmental defects and have been reported in various ethnic groups. The purpose of this study was to investigate the clinical features of optic Nerve Malformation caused by PAX6 mutations in Indian patients. Methods: Total genomic DNA was isolated from peripheral blood of 27 sporadic probands affected with congenital optic Nerve Malformation, unaffected family members, and 50 unrelated age-matched controls. Informed consent was obtained from all study subjects. Polymerase chain reaction was carried out to explore PAX6 defective alleles using single-strand conformation analysis (PCR-SSCA) followed by automated bidirectional sequencing. Results: We identified two novel PAX6 missense mutations in two unrelated sporadic probands. The mutation analysis revealed variation at position c.469G>C, codon 36 in proband ONH 4-1 with optic Nerve hypoplasia. The other de novo mutation was observed at c.514G>C, codon 51 in proband ODC 5-1 with optic disc coloboma. Both G>C base substitutions cause a relatively conservative amino acid change, altering glycine to alanine residues within the paired DNAbinding domain. Conclusions: In this study, we have been able to identify two sequence variations in the PAX6 gene. These missense mutations may uniquely alter the structure and expression of PAX6 protein, resulting in distinct clinical phenotypes. Mutation analysis of 27 probands for PAX6 has resulted in only two significant variants. This finding demonstrated that the frequency of PAX6 mutations associated with optic Nerve Malformation is low, requiring the elucidation of other candidate genes in other patients.
Masanori Adachi - One of the best experts on this subject based on the ideXlab platform.
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combined pituitary hormone deficiency with unique pituitary dysplasia and morning glory syndrome related to a heterozygous prokr2 mutation
Clinical Pediatric Endocrinology, 2015Co-Authors: Yumi Asakura, Koji Muroya, Junko Hanakawa, Takeshi Sato, Noriko Aida, Satoshi Narumi, Tomonobu Hasegawa, Masanori AdachiAbstract:Recent reports have indicated the role of the prokineticin receptor 2 gene (PROKR2) in the etiology of congenital hypopituitarism, including septo-optic dysplasia and Kallmann syndrome. In the present study, using next-generation targeted sequencing, we identified a novel heterozygous PROKR2 variant (c.742C>T; p.R248W) in a female patient who had combined pituitary hormone deficiency (CPHD), morning glory syndrome and a severely malformed pituitary gland. No other mutation was present in 27 genes related to hypogonadotropic hypogonadism, pituitary hormone deficiency and optic Nerve Malformation. The substituted amino acid was located on the third intracellular loop of the PROKR2 protein, which is a G protein-coupled receptor. Computational analyses with two programs (SIFT and PolyPhen-2) showed that the substitution was deleterious to PROKR2 function. The p.R248W mutation was transmitted from the patient's mother, who had a slightly delayed menarche. Collectively, we provide further genetic evidence linking heterozygous PROKR2 mutations and the development of CPHD.
Yi Liu - One of the best experts on this subject based on the ideXlab platform.
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establishment of a human ipsc line sdqlchi010 a from a patient with optic Nerve Malformation carrying a heterozygous mutation in pax6 gene
Stem Cell Research, 2019Co-Authors: Haiyan Zhang, Xiaomeng Yang, Jingyun Guan, Rui Dong, Zhongtao Gai, Yi LiuAbstract:We established an induced pluripotent stem cell (iPSC) line (SDQLCHi010-A) from peripheral blood mononuclear cells isolated from a 4-year-old boy with optic Nerve Malformation and intellectual disability carrying a heterozygous mutation (c.220A>G (p.S74G)) in PAX6 gene. Non-integrating episomal vectors containing OCT4, SOX2, KLF4, BCL-XL and MYC were used for reprogramming. The established iPSC line showed normal karyotype, expressed pluripotency markers, exhibited differentiation potential in vitro and kept PAX6 gene mutation.
Jeyabalan Nallathambi - One of the best experts on this subject based on the ideXlab platform.
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pax6 missense mutations associated in patients with optic Nerve Malformation
Molecular Vision, 2006Co-Authors: Jeyabalan Nallathambi, Guruswamy Neethirajan, Shetty Shashikant, P Vijayalakshmi, Periasamy SundaresanAbstract:Purpose: PAX6 missense mutations are likely to cause a spectrum of ocular, neurological, and systemic developmental defects and have been reported in various ethnic groups. The purpose of this study was to investigate the clinical features of optic Nerve Malformation caused by PAX6 mutations in Indian patients. Methods: Total genomic DNA was isolated from peripheral blood of 27 sporadic probands affected with congenital optic Nerve Malformation, unaffected family members, and 50 unrelated age-matched controls. Informed consent was obtained from all study subjects. Polymerase chain reaction was carried out to explore PAX6 defective alleles using single-strand conformation analysis (PCR-SSCA) followed by automated bidirectional sequencing. Results: We identified two novel PAX6 missense mutations in two unrelated sporadic probands. The mutation analysis revealed variation at position c.469G>C, codon 36 in proband ONH 4-1 with optic Nerve hypoplasia. The other de novo mutation was observed at c.514G>C, codon 51 in proband ODC 5-1 with optic disc coloboma. Both G>C base substitutions cause a relatively conservative amino acid change, altering glycine to alanine residues within the paired DNAbinding domain. Conclusions: In this study, we have been able to identify two sequence variations in the PAX6 gene. These missense mutations may uniquely alter the structure and expression of PAX6 protein, resulting in distinct clinical phenotypes. Mutation analysis of 27 probands for PAX6 has resulted in only two significant variants. This finding demonstrated that the frequency of PAX6 mutations associated with optic Nerve Malformation is low, requiring the elucidation of other candidate genes in other patients.
Yumi Asakura - One of the best experts on this subject based on the ideXlab platform.
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combined pituitary hormone deficiency with unique pituitary dysplasia and morning glory syndrome related to a heterozygous prokr2 mutation
Clinical Pediatric Endocrinology, 2015Co-Authors: Yumi Asakura, Koji Muroya, Junko Hanakawa, Takeshi Sato, Noriko Aida, Satoshi Narumi, Tomonobu Hasegawa, Masanori AdachiAbstract:Recent reports have indicated the role of the prokineticin receptor 2 gene (PROKR2) in the etiology of congenital hypopituitarism, including septo-optic dysplasia and Kallmann syndrome. In the present study, using next-generation targeted sequencing, we identified a novel heterozygous PROKR2 variant (c.742C>T; p.R248W) in a female patient who had combined pituitary hormone deficiency (CPHD), morning glory syndrome and a severely malformed pituitary gland. No other mutation was present in 27 genes related to hypogonadotropic hypogonadism, pituitary hormone deficiency and optic Nerve Malformation. The substituted amino acid was located on the third intracellular loop of the PROKR2 protein, which is a G protein-coupled receptor. Computational analyses with two programs (SIFT and PolyPhen-2) showed that the substitution was deleterious to PROKR2 function. The p.R248W mutation was transmitted from the patient's mother, who had a slightly delayed menarche. Collectively, we provide further genetic evidence linking heterozygous PROKR2 mutations and the development of CPHD.