Novel WNT1 mutations in children with osteogenesis imperfecta: Clinical and functional characterization

Li, Yanqin; Ren, Xiu Bao; Wang, Yanzhou; Bardai, Ghalib; Sturm, Marc; Dai, Yun-Zhang; Rieß, Olaf; Zhang, Yao; Li, Hu; Li, Tianyou; Zhai, Naixiang; Zhang, Jian; Rauch, Frank; Han, Jinxiang

doi:10.1016/j.bone.2018.06.018

Cited by 26 publications

(29 citation statements)

References 25 publications

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“…Bluish sclerae were not observed in our patient cohort, but have been noted in a few patients with bi‐allelic‐ WNT1 mutations (9/34, 26.5%; Supporting Information Table S1). Hearing and tooth development are usually not impaired (Aldinger et al, ; Fahiminiya et al, ; Faqeih et al, ; Keupp et al, ; Kuptanon et al, ; Laine et al, ; Lu et al, ; Pyott et al, ; Umair et al, ; Won et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…The cause of ptosis is currently unknown. It has been noted that some patients with bi‐allelic WNT1 mutations have neurological/brain abnormalities (6/11, 54.5%), including abnormalities of the midbrain and/or cerebellum, and/or severe developmental/intellectual delay (11/28, 39.3%; Aldinger et al, ; Fahiminiya et al, ; Faqeih et al, ; Keupp et al, ; Kuptanon et al, ; Laine et al, ; Lu et al, ; Pyott et al, ; Umair et al, ; Won et al, ). Brain images for our cohort were available for only one patient (PVIII, presenting with severe brain anomalies, Figure v) and four patients had a significant delay in cognitive development (4/10, 40%).…”

Section: Discussionmentioning

confidence: 99%

“…Homozygous and compound heterozygous mutations in WNT1 have been identified in a series of patients displaying moderate to severe AR forms of OI (compatible with OI type III or IV according to the Sillence classification; Aldinger et al, ; Fahiminiya et al, ; Faqeih, Shaheen, & Alkuraya, ; Keupp et al, ; Kuptanon et al, ; Laine et al, ; Lu et al, ; Pyott et al, ; Umair et al, ; Won et al, ). This type of OI is currently classified as OI type XV (Forlino & Marini, ; Kang et al, ; Marini et al, ; Sillence, Senn, & Danks, ).…”

Section: Introductionmentioning

confidence: 99%

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Ptosis as a unique hallmark for autosomal recessive WNT1‐associated osteogenesis imperfecta

Nampoothiri

Guillemyn

Elçioğlu

et al. 2019

American J of Med Genetics Pt A

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Osteogenesis imperfecta (OI) is a heritable connective tissue disorder, mainly characterized by bone fragility and low bone mass. Defects in the type I procollagen-encoding genes account for the majority of OI, but increasingly more rare autosomal recessive (AR) forms are being identified, which are caused by defects in genes involved in collagen metabolism, bone mineralization, or osteoblast differentiation. Bi-allelic mutations in WNT1 have been associated with a rare form of AR OI, characterized by severe osteoporosis, vertebral compression, scoliosis, fractures, short stature, and variable neurological problems. Heterozygous WNT1 mutations have been linked to autosomal dominant early-onset osteoporosis. In this study, we describe the clinical and molecular findings in 10 new patients with AR WNT1-related OI. Thorough revision of the clinical symptoms of these 10 novel patients and previously published AR WNT1 OI cases highlight ptosis as a unique hallmark in the diagnosis of this OI subtype. K E Y W O R D Scollagen, osteogenesis imperfecta, ptosis, WNT1

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ptosis as a unique hallmark for autosomal recessive WNT1‐associated osteogenesis imperfecta

Nampoothiri

Guillemyn

Elçioğlu

et al. 2019

American J of Med Genetics Pt A

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“…OI/EDS patients with this type of mutation usually presented mainly by generalized joint hyperlaxity and skin hyperextensibility, early progressive scoliosis as well as mild to lethal OI symptoms including relatively short stature, blue sclerae, infrequent or frequent bone fracture and different levels of osteopenia ( Figure 3) (89)(90)(91)93). We found ptosis in one individual with family history existed in OI/ EDS with the mutation of c.3521C>T (Ala1174Val) in COL1A1; this symptom is also displayed in type XV OI caused by the Wnt1 gene (95)(96)(97).…”

Section: Oi/edsmentioning

confidence: 63%

Molecular mechanisms and clinical manifestations of rare genetic disorders associated with type I collagen

Zhang

Wang

et al. 2019

IRDR

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Type I collagen is an important structural protein of bone, skin, tendon, ligament and other connective tissues. It is initially synthesized as a precursor form, procollagen, consisting of two identical pro-α1(I) and one proα2(I) chains, encoded by COL1A1 and COL1A2, respectively. The N-and C-terminal propeptides of procollagen are cleavage by N-proteinase and C-proteinase correspondingly, to form the central triple helix structure with Gly-X-Y repeat units. Mutations of COL1A1 and COL1A2 genes are associated with osteogenesis imperfecta, some types of Ehlers-Danlos syndrome, Caffey diseases, and osteogenesis imperfect/Ehlers-Danlos syndrome overlapping diseases. Clinical symptoms caused by different variations can be variable or similar, mild to lethal, and vice versa. We reviewed the relationship between clinical manifestations and type I collagen -related rare genetic disorders and their possible molecular mechanisms for different mutations and disorders.

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“…Osteogenesis imperfecta (OI), also called brittle bone disease, is a genetic connective tissue disorder with a broad phenotypic variation and genetic heterozygosity. Autosomal dominant mutations in COL1A1 and COL1A2 are the main cause of classic osteogenesis imperfecta, which is characterized by bone fragility, blue sclerae, defects in the teeth, and deficits in hearing and vision (1)(2)(3). Epidemiological data on OI varies greatly, with an average prevalence of 1 in 15,000 to 20,000 births worldwide (4).…”

Section: Introductionmentioning

confidence: 99%

Splice receptor-site mutation c.697-2A>G of the <i>COL1A1</i> gene in a Chinese family with osteogenesis imperfecta

Zhai

Wang

et al. 2019

IRDR

Self Cite

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Novel WNT1 mutations in children with osteogenesis imperfecta: Clinical and functional characterization

Cited by 26 publications

References 25 publications

Ptosis as a unique hallmark for autosomal recessive WNT1‐associated osteogenesis imperfecta

Ptosis as a unique hallmark for autosomal recessive WNT1‐associated osteogenesis imperfecta

Molecular mechanisms and clinical manifestations of rare genetic disorders associated with type I collagen

Splice receptor-site mutation c.697-2A>G of the <i>COL1A1</i> gene in a Chinese family with osteogenesis imperfecta

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