Limits...
Genotype and phenotype analysis of Taiwanese patients with osteogenesis imperfecta.

Lin HY, Chuang CK, Su YN, Chen MR, Chiu HC, Niu DM, Lin SP - Orphanet J Rare Dis (2015)

Bottom Line: Fifteen (41%) were novel mutations, and twelve (32%) were familial mutations.Twenty-nine patients had helical mutations (caused by the substitution of a glycine within the Gly-X-Y triplet domain of the triple helix), and 42 had haploinsufficiency mutations (caused by frameshift, nonsense, and splice-site mutations).Genotype and phenotype databases are expected to promote better genetic counseling and medical care of patients with OI.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.

ABSTRACT

Background: Osteogenesis imperfecta (OI) is a congenital disorder characterized by increased bone fragility and low bone mass.

Methods: The presence of COL1A1 or COL1A2 mutation was investigated by direct sequencing in 72 patients with OI type I, III, or IV (27 males and 45 females; age range 0.2-62 years) from 37 unrelated families. The clinical features of these patients were also recorded.

Results: Thirty-seven COL1A1 and COL1A2 mutations were identified, including 28 COL1A1 mutations and 9 COL1A2 mutations. Fifteen (41%) were novel mutations, and twelve (32%) were familial mutations. A review of their medical records revealed that the 72 patients could be classified into OI type I (n = 42), III (n = 5), and IV (n = 25). Twenty-nine patients had helical mutations (caused by the substitution of a glycine within the Gly-X-Y triplet domain of the triple helix), and 42 had haploinsufficiency mutations (caused by frameshift, nonsense, and splice-site mutations). Compared with haploinsufficiency, the patients with helical mutations had more severely impaired skeletal phenotypes, including shorter height, lower bone mineral density, poorer walking ability, more frequent manifestations of dentinogenesis imperfecta and scoliosis (p < 0.05).

Conclusions: Genotype and phenotype databases are expected to promote better genetic counseling and medical care of patients with OI.

Show MeSH

Related in: MedlinePlus

Relationships between age and a height SDS (n = 71), b BMD SDS (n = 64) of different mutation types [COL1A1/COL1A2 helical glycine mutation (blue dot) vs. COL1A1 haploinsufficiency mutation (pink dot)] in patients with osteogenesis imperfecta. SDS, standard deviation score; BMD, bone mineral density
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4666204&req=5

Fig1: Relationships between age and a height SDS (n = 71), b BMD SDS (n = 64) of different mutation types [COL1A1/COL1A2 helical glycine mutation (blue dot) vs. COL1A1 haploinsufficiency mutation (pink dot)] in patients with osteogenesis imperfecta. SDS, standard deviation score; BMD, bone mineral density

Mentions: The OI type was correlated with mutated genes and mutation types. Compared with COL1A2 mutations, COL1A1 mutations were more frequent in the patients with OI type I (46 % vs. 33 %) and III (14 % vs. 11 %), and less frequent in the patients with OI type IV (39 % vs. 56 %). Helical mutations were more frequent in the patients with OI type III (27 % vs. 5 %) and IV (47 % vs. 38 %), and less frequent in the patients with OI type I (27 % vs. 57 %) compared to those with haploinsufficiency mutations (Table 3). Among the 72 patients, 51 had a COL1A1 mutation and 21 had a COL1A2 mutation. Twenty-nine patients had helical mutations and 42 had haploinsufficiency mutations. Compared with haploinsufficiency, the patients with helical mutations had more severely damaged skeletal phenotypes, including shorter height, lower weight and BMD, poorer walking ability, and more frequent manifestations of DI and scoliosis (p < 0.05) (Table 4, Fig: 1a and b).Table 3


Genotype and phenotype analysis of Taiwanese patients with osteogenesis imperfecta.

Lin HY, Chuang CK, Su YN, Chen MR, Chiu HC, Niu DM, Lin SP - Orphanet J Rare Dis (2015)

Relationships between age and a height SDS (n = 71), b BMD SDS (n = 64) of different mutation types [COL1A1/COL1A2 helical glycine mutation (blue dot) vs. COL1A1 haploinsufficiency mutation (pink dot)] in patients with osteogenesis imperfecta. SDS, standard deviation score; BMD, bone mineral density
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4666204&req=5

Fig1: Relationships between age and a height SDS (n = 71), b BMD SDS (n = 64) of different mutation types [COL1A1/COL1A2 helical glycine mutation (blue dot) vs. COL1A1 haploinsufficiency mutation (pink dot)] in patients with osteogenesis imperfecta. SDS, standard deviation score; BMD, bone mineral density
Mentions: The OI type was correlated with mutated genes and mutation types. Compared with COL1A2 mutations, COL1A1 mutations were more frequent in the patients with OI type I (46 % vs. 33 %) and III (14 % vs. 11 %), and less frequent in the patients with OI type IV (39 % vs. 56 %). Helical mutations were more frequent in the patients with OI type III (27 % vs. 5 %) and IV (47 % vs. 38 %), and less frequent in the patients with OI type I (27 % vs. 57 %) compared to those with haploinsufficiency mutations (Table 3). Among the 72 patients, 51 had a COL1A1 mutation and 21 had a COL1A2 mutation. Twenty-nine patients had helical mutations and 42 had haploinsufficiency mutations. Compared with haploinsufficiency, the patients with helical mutations had more severely damaged skeletal phenotypes, including shorter height, lower weight and BMD, poorer walking ability, and more frequent manifestations of DI and scoliosis (p < 0.05) (Table 4, Fig: 1a and b).Table 3

Bottom Line: Fifteen (41%) were novel mutations, and twelve (32%) were familial mutations.Twenty-nine patients had helical mutations (caused by the substitution of a glycine within the Gly-X-Y triplet domain of the triple helix), and 42 had haploinsufficiency mutations (caused by frameshift, nonsense, and splice-site mutations).Genotype and phenotype databases are expected to promote better genetic counseling and medical care of patients with OI.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.

ABSTRACT

Background: Osteogenesis imperfecta (OI) is a congenital disorder characterized by increased bone fragility and low bone mass.

Methods: The presence of COL1A1 or COL1A2 mutation was investigated by direct sequencing in 72 patients with OI type I, III, or IV (27 males and 45 females; age range 0.2-62 years) from 37 unrelated families. The clinical features of these patients were also recorded.

Results: Thirty-seven COL1A1 and COL1A2 mutations were identified, including 28 COL1A1 mutations and 9 COL1A2 mutations. Fifteen (41%) were novel mutations, and twelve (32%) were familial mutations. A review of their medical records revealed that the 72 patients could be classified into OI type I (n = 42), III (n = 5), and IV (n = 25). Twenty-nine patients had helical mutations (caused by the substitution of a glycine within the Gly-X-Y triplet domain of the triple helix), and 42 had haploinsufficiency mutations (caused by frameshift, nonsense, and splice-site mutations). Compared with haploinsufficiency, the patients with helical mutations had more severely impaired skeletal phenotypes, including shorter height, lower bone mineral density, poorer walking ability, more frequent manifestations of dentinogenesis imperfecta and scoliosis (p < 0.05).

Conclusions: Genotype and phenotype databases are expected to promote better genetic counseling and medical care of patients with OI.

Show MeSH
Related in: MedlinePlus