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Identification of a novel COL2A1 mutation (c.1744G>A) in a Japanese family: a case report.

Kishiya M, Nakamura Y, Ohishi H, Furukawa K, Ishibashi Y - J Med Case Rep (2014)

Bottom Line: Mutations in the gene encoding the type II collagen gene (COL2A1) have been found to affect the entire skeletal system.Based on these findings, haplotype analysis of her and her family members was performed by examining select candidate genes from the critical interval for epiphyseal dysplasia of the femoral head on 12q13 and sequencing the promoter and exonic regions of COL2A1.A novel COL2A1 mutation (c.1744G>A) was identified within one Japanese family.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan. kishiya@isis.ocn.ne.jp.

ABSTRACT

Introduction: Mutations in the gene encoding the type II collagen gene (COL2A1) have been found to affect the entire skeletal system. Recently, inheritable skeletal dysplasia caused by novel COL2A1 mutations has been linked to an inherited disease of the hip joint that neither involves the entire skeletal system nor is characterized by the presence of concomitant disorders, such as spinal or ocular abnormalities.

Case presentation: A 27-year-old Japanese woman previously diagnosed with avasucular necrosis (AVN) of the femoral head on the basis of radiological findings was referred to the study site for surgical management of a painful hip joint. She had no history of disease but suffered from bilateral hip joint lesions. Analysis of her pedigree revealed that bilateral hip joint lesions affected more than three generations of her family. Based on these findings, haplotype analysis of her and her family members was performed by examining select candidate genes from the critical interval for epiphyseal dysplasia of the femoral head on 12q13 and sequencing the promoter and exonic regions of COL2A1.

Conclusion: A novel COL2A1 mutation (c.1744G>A) was identified within one Japanese family.

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Related in: MedlinePlus

Real-time polymerase chain reaction analysis of our patient’s family and a normal control. Probe-adapted real-time PCR analysis using cycling probe technology led to the detection of a single nucleic acid polymorphism (SNP) in a target DNA sequence in our patient’s father and grandmother. For SNP typing, two cycling probes labeled with two different fluorescent dyes (6-carboxyfluorescein (FAM) or 6-carboxy-X-rhodamine (ROX)) were used, with each probe harboring ribonucleic acid (RNA) corresponding to the wild-type nucleotide or the nucleotide with a mutation at the SNP position. Expression analysis of our patient (A), her father (B) and her grandmother (C) shows a G→A transition of COL2A1 (c.1744G>A), while expression analysis of her mother (D) and a normal control (E) shows no mutation in the COL2A1 coding region.
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Figure 9: Real-time polymerase chain reaction analysis of our patient’s family and a normal control. Probe-adapted real-time PCR analysis using cycling probe technology led to the detection of a single nucleic acid polymorphism (SNP) in a target DNA sequence in our patient’s father and grandmother. For SNP typing, two cycling probes labeled with two different fluorescent dyes (6-carboxyfluorescein (FAM) or 6-carboxy-X-rhodamine (ROX)) were used, with each probe harboring ribonucleic acid (RNA) corresponding to the wild-type nucleotide or the nucleotide with a mutation at the SNP position. Expression analysis of our patient (A), her father (B) and her grandmother (C) shows a G→A transition of COL2A1 (c.1744G>A), while expression analysis of her mother (D) and a normal control (E) shows no mutation in the COL2A1 coding region.

Mentions: Haplotype analysis of the family members was performed by examining select candidate genes from the critical interval for epiphyseal dysplasia of the femoral head on 12q13. The entire coding regions of COL2A1, along with the flanking intronic regions, were amplified by polymerase chain reaction (PCR) using the Ex Taq™ system with an ABI PRISM® 3100 Genetic Analyzer (Applied Biosystems, Foster, CA, USA) and a BigDye® Terminator Cycle Sequencing Kit (Applied Biosystems). The complementary deoxyribonucleic acid (cDNA) sequence of COL2A1 was obtained from GenBank (accession no. NM_001844.4). For cDNA numbering, +1 corresponds to the A of the ATG translation initiation codon 1 in the reference sequence (Figure 7). A G→A transition of COL2A1 (c.1744G>A (p.Gly582Ser)) was detected in the affected member in each of the three generations of the family (Figures 8 and9). This transition predicts the replacement of glycine with serine in COL2A1. Based on this finding, members of the family were diagnosed with inherited epiphyseal dysplasia located on the femoral head. For those three affected members in whom autosomal dominant inheritance of the disease was strongly suspected (IV-1, III-20, II-9), the chromosomal position of the gene to COL2A1 (c.1744G>A (p.Gly582Ser)) was mapped. No mutation was detected in the COL2A1 coding region of the mother or in a normal control (Figure 9).


Identification of a novel COL2A1 mutation (c.1744G>A) in a Japanese family: a case report.

Kishiya M, Nakamura Y, Ohishi H, Furukawa K, Ishibashi Y - J Med Case Rep (2014)

Real-time polymerase chain reaction analysis of our patient’s family and a normal control. Probe-adapted real-time PCR analysis using cycling probe technology led to the detection of a single nucleic acid polymorphism (SNP) in a target DNA sequence in our patient’s father and grandmother. For SNP typing, two cycling probes labeled with two different fluorescent dyes (6-carboxyfluorescein (FAM) or 6-carboxy-X-rhodamine (ROX)) were used, with each probe harboring ribonucleic acid (RNA) corresponding to the wild-type nucleotide or the nucleotide with a mutation at the SNP position. Expression analysis of our patient (A), her father (B) and her grandmother (C) shows a G→A transition of COL2A1 (c.1744G>A), while expression analysis of her mother (D) and a normal control (E) shows no mutation in the COL2A1 coding region.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4150419&req=5

Figure 9: Real-time polymerase chain reaction analysis of our patient’s family and a normal control. Probe-adapted real-time PCR analysis using cycling probe technology led to the detection of a single nucleic acid polymorphism (SNP) in a target DNA sequence in our patient’s father and grandmother. For SNP typing, two cycling probes labeled with two different fluorescent dyes (6-carboxyfluorescein (FAM) or 6-carboxy-X-rhodamine (ROX)) were used, with each probe harboring ribonucleic acid (RNA) corresponding to the wild-type nucleotide or the nucleotide with a mutation at the SNP position. Expression analysis of our patient (A), her father (B) and her grandmother (C) shows a G→A transition of COL2A1 (c.1744G>A), while expression analysis of her mother (D) and a normal control (E) shows no mutation in the COL2A1 coding region.
Mentions: Haplotype analysis of the family members was performed by examining select candidate genes from the critical interval for epiphyseal dysplasia of the femoral head on 12q13. The entire coding regions of COL2A1, along with the flanking intronic regions, were amplified by polymerase chain reaction (PCR) using the Ex Taq™ system with an ABI PRISM® 3100 Genetic Analyzer (Applied Biosystems, Foster, CA, USA) and a BigDye® Terminator Cycle Sequencing Kit (Applied Biosystems). The complementary deoxyribonucleic acid (cDNA) sequence of COL2A1 was obtained from GenBank (accession no. NM_001844.4). For cDNA numbering, +1 corresponds to the A of the ATG translation initiation codon 1 in the reference sequence (Figure 7). A G→A transition of COL2A1 (c.1744G>A (p.Gly582Ser)) was detected in the affected member in each of the three generations of the family (Figures 8 and9). This transition predicts the replacement of glycine with serine in COL2A1. Based on this finding, members of the family were diagnosed with inherited epiphyseal dysplasia located on the femoral head. For those three affected members in whom autosomal dominant inheritance of the disease was strongly suspected (IV-1, III-20, II-9), the chromosomal position of the gene to COL2A1 (c.1744G>A (p.Gly582Ser)) was mapped. No mutation was detected in the COL2A1 coding region of the mother or in a normal control (Figure 9).

Bottom Line: Mutations in the gene encoding the type II collagen gene (COL2A1) have been found to affect the entire skeletal system.Based on these findings, haplotype analysis of her and her family members was performed by examining select candidate genes from the critical interval for epiphyseal dysplasia of the femoral head on 12q13 and sequencing the promoter and exonic regions of COL2A1.A novel COL2A1 mutation (c.1744G>A) was identified within one Japanese family.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan. kishiya@isis.ocn.ne.jp.

ABSTRACT

Introduction: Mutations in the gene encoding the type II collagen gene (COL2A1) have been found to affect the entire skeletal system. Recently, inheritable skeletal dysplasia caused by novel COL2A1 mutations has been linked to an inherited disease of the hip joint that neither involves the entire skeletal system nor is characterized by the presence of concomitant disorders, such as spinal or ocular abnormalities.

Case presentation: A 27-year-old Japanese woman previously diagnosed with avasucular necrosis (AVN) of the femoral head on the basis of radiological findings was referred to the study site for surgical management of a painful hip joint. She had no history of disease but suffered from bilateral hip joint lesions. Analysis of her pedigree revealed that bilateral hip joint lesions affected more than three generations of her family. Based on these findings, haplotype analysis of her and her family members was performed by examining select candidate genes from the critical interval for epiphyseal dysplasia of the femoral head on 12q13 and sequencing the promoter and exonic regions of COL2A1.

Conclusion: A novel COL2A1 mutation (c.1744G>A) was identified within one Japanese family.

Show MeSH
Related in: MedlinePlus