Complex heterozygous &lt;i&gt;WNT1&lt;/i&gt; mutation in severe recessive osteogenesis imperfecta of a Chinese patient

Li, Yanqin; Dai, Yun-Zhang; Wang, Yanzhou; Zhai, Naixiang; Zhang, Jian; Liu, Junlong; Yin, Xiaoli; Li, Tianyou; Ren, Xiu Bao; Han, Jinxiang

doi:10.5582/irdr.2018.01014

Cited by 7 publications

(2 citation statements)

References 30 publications

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“…WNT1 pathogenic variants impair b-Catenin translocation affecting osteoblast function and peak bone mass (28,29). WNT1 pathogenic variants described so far (Figure 3) are associated with different pictures of bone fragility according to whether the variant was heterozygous or homozygous (13)(14)(15)(16)(17)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46). In fact, patients carrying heterozygous variants exhibit normal growth, reduced bone mass or early-onset osteoporosis and fractures without appendicular deformities (13-15, 42) (Table 3), whereas those carrying homozygous variants display a life-threatening phenotype due to severe bone deformities (12)(13)(14)19).…”

Section: Discussionmentioning

confidence: 99%

Case report: Early-onset osteoporosis in a patient carrying a novel heterozygous variant of the WNT1 gene

et al. 2022

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The WNT1 gene is crucial for bone development and homeostasis. Homozygous mutations in WNT1 cause severe bone fragility known as osteogenesis imperfecta type XV. Moreover, heterozygous WNT1 mutations have been found in adults with early-onset osteoporosis. We identified a 35 year-old Caucasian woman who experienced multiple vertebral fractures two months after her second pregnancy. There was no history of risk factors for secondary osteoporosis or family history of osteoporosis. Dual-energy X-ray absorptiometry confirmed a marked reduction of bone mineral density (BMD) at the lumbar spine (0.734 g/cm2, Z-score -2.8), femoral neck (0.48 g/cm2, Z-score -3.5), and total hip (0.589 g/cm2, Z-score -3.0). Blood tests excluded secondary causes of bone fragility. Genetic analysis revealed a heterozygous missense mutation (p.Leu370Val) in the WNT1 gene. Varsome classified it as a variant of uncertain significance. However, the fact that the Leucine residue at position 370 is highly conserved among vertebrate species and the variant has a very low allelic frequency in the general population would exclude the possibility of a polymorphism. The patient was treated for two years with teriparatide therapy associated with calcium and vitamin D supplements. During the follow-up period she did not report further clinical fractures. After 24 months of teriparatide, BMD increased at lumbar spine (+14.6%), femoral neck (+8.3%) and total hip (+4.9%) compared to baseline. We confirm that the heterozygous WNT1 mutation could cause a variable bone fragility and low turnover osteoporosis. We suggest that teriparatide is one of the most appropriate available therapies for this case.

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Section: Discussionmentioning

confidence: 99%

Case report: Early-onset osteoporosis in a patient carrying a novel heterozygous variant of the WNT1 gene

et al. 2022

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“…The pathogenic variant c.677C >T (p.S226L), which changes amino acid 226 from serine to leucine, is a missense variant. According to the Human Gene Mutation Database (HGMD), it may result in the development of type XV OI (8,12). Another known missense mutation is c.620G>A (p.R207H), which results from a change in amino acid 207 from arginine to histidine.…”

Section: Experience and Insightsmentioning

confidence: 99%

Type XV osteogenesis imperfecta: A novel mutation in the <i>WNT1 </i>gene, c.620G >A (p.R207H), is associated with an inner ear deformity

Zhu

et al. 2023

IRDR

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type XV osteogenesis imperfecta, heterozygous mutation, WNT1, inner ear dysplasiaThe Wnt signaling pathway is vital in encouraging bone growth. WNT1 gene mutations have been identified as the major cause of type XV osteogenesis imperfecta (OI). Described here is a case of complex heterozygous WNT1 c.620G>A (p.R207H) and c.677C >T (p.S226L) OI caused by a novel mutation at locus c.620G >A (p.R207H). The female patient had type XV OI, distinguished by poor bone density, frequent fractures, a small stature, skull softening, lack of dentine hypoplasia, a brain malformation, and obvious blue sclera. A CT scan of the temporal bone revealed abnormalities of the inner ear, necessitating a hearing aid 8 months after birth. There was no family history of such disorders in the proband's parents. The proband inherited complex heterozygous WNT1 gene variants c.677C>T (p.S226L) and c.620G>A (p.R207H) from her father and mother, respectively. Presented here is a case of OI with inner ear deformation caused by c.620G>A (p.R207H), which is a novel WNT1 site mutation. This case broadens the genetic spectrum of OI and it provides a rationale for genetic testing of mothers and a medical consultation to estimate the risk of fetal illness.

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Exome sequencing identified mutations in the WNT1 and COL1A2 genes in osteogenesis imperfecta cases

Mehta,

Vishvkarma,

Gupta

et al. 2024

Mol Biol Rep

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Complex heterozygous <i>WNT1</i> mutation in severe recessive osteogenesis imperfecta of a Chinese patient

Cited by 7 publications

References 30 publications

Case report: Early-onset osteoporosis in a patient carrying a novel heterozygous variant of the WNT1 gene

Case report: Early-onset osteoporosis in a patient carrying a novel heterozygous variant of the WNT1 gene

Type XV osteogenesis imperfecta: A novel mutation in the <i>WNT1 </i>gene, c.620G >A (p.R207H), is associated with an inner ear deformity

Exome sequencing identified mutations in the WNT1 and COL1A2 genes in osteogenesis imperfecta cases

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