Lack of correlation between the type of COL1A1 or COL1A2 mutation and hearing loss in osteogenesis imperfecta patients

Hartikka, Heini; Kuurila, Kaija; Körkkö, Jarmo; Kaitila, Ilkka; Grénman, Reidar; Pynnönen, Seppo; Hyland, James; Ala‐Kokko, Leena

doi:10.1002/humu.20108

Cited by 36 publications

(49 citation statements)

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“…The spectrum of collagen I mutations causing OI was similar to other studied cohorts, and support previously presented regional models for genotype-phenotype correlations. 15,29,30 Qualitative mutations affecting COL1A1 are more often lethal than mutations located in COL1A2 (36 vs 20%). 15 In accordance with this, our data confirmed that the clinical phenotype concerning lumbar spine BMD, height, peripheral fracture rate, the presence of vertebral compression fractures, intramedullary rodding, and OI type was more severe for serine substitutions in the α1-compared with the α2-chain.…”

Section: Noteworthy Mutationsmentioning

confidence: 99%

Genetic epidemiology, prevalence, and genotype–phenotype correlations in the Swedish population with osteogenesis imperfecta

et al. 2015

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Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder, caused by collagen I mutations in 90% of cases. There are no comprehensive genotype-phenotype studies on 4100 families outside North America, and no population-based studies determining the genetic epidemiology of OI. Here, detailed clinical phenotypes were recorded, and the COL1A1 and COL1A2 genes were analyzed in 164 Swedish OI families (223 individuals). Averages for bone mineral density (BMD), height and yearly fracture rate were calculated and related to OI and mutation type. N-terminal helical mutations in both the α1-and α2-chains were associated with the absence of dentinogenesis imperfecta (Po0.0001 vs 0.0049), while only those in the α1-chain were associated with blue sclera (P = 0.0110). Comparing glycine with serine substitutions, α1-alterations were associated with more severe phenotype (P = 0.0031). Individuals with type I OI caused by qualitative vs quantitative mutations were shorter (Po0.0001), but did not differ considering fractures or BMD. The children in this cohort were estimated to represent 495% of the complete Swedish pediatric OI population. The prevalence of OI types I, III, and IV was 5.16, 0.89, and 1.35/100 000, respectively (7.40/100 000 overall), corresponding to what has been estimated but not unequivocally proven in any population. Collagen I mutation analysis was performed in the family of 97% of known cases, with causative mutations found in 87%. Qualitative mutations caused 32% of OI type I. The data reported here may be helpful to predict phenotype, and describes for the first time the genetic epidemiology in 495% of an entire OI population.

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Section: Noteworthy Mutationsmentioning

confidence: 99%

Genetic epidemiology, prevalence, and genotype–phenotype correlations in the Swedish population with osteogenesis imperfecta

et al. 2015

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“…Half of patients with osteogenesis imper fecta develop hearing loss, usually between the second and fourth decades of life 190,191 . Conductive deafness is frequently associated with bony changes that affect the oval window region and lead to stapes footplate fixation due to thinning, atrophy and fractures of the stapes and the incus 192 .…”

Section: Cardiovascular Manifestationsmentioning

confidence: 99%

Osteogenesis imperfecta

Marini

Forlino

Bächinger

et al. 2017

Nat Rev Dis Primers

543

582

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| Skeletal deformity and bone fragility are the hallmarks of the brittle bone dysplasia osteogenesis imperfecta. The diagnosis of osteogenesis imperfecta usually depends on family history and clinical presentation characterized by a fracture (or fractures) during the prenatal period, at birth or in early childhood; genetic tests can confirm diagnosis. Osteogenesis imperfecta is caused by dominant autosomal mutations in the type I collagen coding genes (COL1A1 and COL1A2) in about 85% of individuals, affecting collagen quantity or structure. In the past decade, (mostly) recessive, dominant and X-linked defects in a wide variety of genes encoding proteins involved in type I collagen synthesis, processing, secretion and post-translational modification, as well as in proteins that regulate the differentiation and activity of bone-forming cells have been shown to cause osteogenesis imperfecta. The large number of causative genes has complicated the classic classification of the disease, and although a new genetic classification system is widely used, it is still debated. Phenotypic manifestations in many organs, in addition to bone, are reported, such as abnormalities in the cardiovascular and pulmonary systems, skin fragility, muscle weakness, hearing loss and dentinogenesis imperfecta. Management involves surgical and medical treatment of skeletal abnormalities, and treatment of other complications. More innovative approaches based on gene and cell therapy, and signalling pathway alterations, are under investigation. NATURE REVIEWS | DISEASE PRIMERS VOLUME 3 | ARTICLE NUMBER 17052 | 1 PRIMER © 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .In this Primer, we provide an overview of epidemio logy, genetics and pathophysiology of osteogenesis imperfecta, as well as diagnosis and management. EpidemiologyStudies from Europe and the United States have found a birth prevalence of osteogenesis imperfecta of 0.3-0.7 per 10,000 births 5,6 . These birth cohort analyses reflect more severe types of osteogenesis imperfecta and do not include more subtle types that become apparent after birth. A population based study that used the Danish National Patient Register found an annual incidence of osteogenesis imperfecta of 1.5 per 10,000 births between 1997 and 2013 (REF. 7). Population surveys in countries with comprehensive medical databases, such as Finland, estimated a prevalence of about 0.5 per 10,000 individ uals 8 , with most having phenotypically milder osteo genesis imperfecta type I and type IV (BOX 1; TABLE 1). Because these birth cohort and population surveys are based on clinical findings and tend to find mutu ally exclusive populations, a reasonable estimate of the incidence of osteogenesis imperfecta is about 1 per 10,000 individuals. Most patients are heterozygous for mutations in COL1A1 or COL1A2. No difference in the prevalence between sexes was reported.Approximately 90% of the 3,000 individuals whose mutations ha...

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“…The expression profiles and characteristics of mutations are influenced by ethnic background. There have been several reports about COL1A1 and COL1A2 mutations in Lithuanian, Finnish, American, Israeli, and Canadian populations (Forlino and Marini, 2000;Glorieux et al, 2000;Hartikka et al, 2004), but they have been restricted to western populations and only a few cases have been reported from Asia, especially in Chinese people.…”

Section: Introductionmentioning

confidence: 99%

Mutation characteristics in type I collagen genes in Chinese patients with osteogenesis imperfecta

Zhong

Ke²,

Zeng³

et al. 2011

Genet. Mol. Res.

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ABSTRACT. Osteogenesis imperfecta is normally caused by an autosomal dominant mutation in the type I collagen genes COL1A1 and COL1A2. The severity of osteogenesis imperfecta varies, ranging from perinatal lethality to a very mild phenotype. Although there have been many reports of COL1A1 and COL1A2 mutations, few cases have been reported in Chinese people. We report on five unrelated families and three sporadic cases. The mutations were detected by PCR and direct sequencing. Four mutations in COL1A1 and one in COL1A2 were found, among which three mutations were previously unreported. The mutation rates of G>C at base 128 in intron 31 of the COL1A1 gene and G>A at base 162 in intron 30 of the COL1A2 gene were higher than normal. The patients' clinical characteristics with the same mutation were variable even in the same family. We conclude that mutations in COL1A1 and COL1A2 also have an important role in osteogenesis imperfecta in the Chinese population. As the Han Chinese people account for a quarter of the world's population, these new data contribute to the type I collagen mutation map.

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Lack of correlation between the type of COL1A1 or COL1A2 mutation and hearing loss in osteogenesis imperfecta patients

Cited by 36 publications

References 0 publications

Genetic epidemiology, prevalence, and genotype–phenotype correlations in the Swedish population with osteogenesis imperfecta

Genetic epidemiology, prevalence, and genotype–phenotype correlations in the Swedish population with osteogenesis imperfecta

Osteogenesis imperfecta

Mutation characteristics in type I collagen genes in Chinese patients with osteogenesis imperfecta

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