The most 5\u2032 truncating homozygous mutation of WNT1 in siblings with osteogenesis imperfecta with a variable degree of brain anomalies: a case report

Chulaluck Kuptanon,Apiruk Sangsin,Dool Kovitvanitcha,Chalurmpon Srichomthong,Kanya Suphapeetiporn,Vorasuk Shotelersuk

doi:10.1186/s12881-018-0639-0

Abstract

BackgroundWNT1 mutations cause bone fragility as well as brain anomalies. There are some reported cases of WNT1 mutations with normal cognition. Genotype and phenotype correlation of WNT1 mutations has not been established.Case presentationHere we present two female siblings with osteogenesis imperfecta (OI) born to a consanguineous couple. Both sustained severe bone deformities. However, only the younger had severe brain anomalies resulting in an early death from pneumonia, while the older had normal intellectual development. Next generation sequencing showed a homozygous mutation, c.6delG, p.Leu3Serfs*36 in WNT1. To our knowledge, it is the most 5′ truncating mutation to date.ConclusionThis report emphasizes the intrafamilial variability of brain anomalies found in this OI type and suggests that WNT1 may not be necessary for normal human cognitive development.

Highlights

Wnt Family Member 1 (WNT1) mutations cause bone fragility as well as brain anomalies
The recessive forms of osteogenesis imperfecta (OI) are caused by mutations in CRTAP, BMP1, CREB3L1, IFITM5, FKBP10, LEPRE1, PPIB, SP7, PLOD2, TMEM38B, SERPINF, SERPINH1, SEC24D, SPARC, WNT1 [1], which lead to defects of proteins interacting with collagen post-translationally
Many OI patients with Collagen type I (COL1A1) or COL1A2 mutations had fractures prenatally but did not have such severe bone deformities in their teens. This emphasizes the fact that onsets of fractures in patients with OI do not correlate with severities of final bone deformities

Summary

Introduction

WNT1 mutations cause bone fragility as well as brain anomalies. There are some reported cases of WNT1 mutations with normal cognition. The natural history of first fractures after birth, but severe bone deformities later in life is similar to the previous reported cases with WNT1 mutations (Table 1: 55%, 10/18). Many OI patients with COL1A1 or COL1A2 mutations had fractures prenatally but did not have such severe bone deformities in their teens. This emphasizes the fact that onsets of fractures in patients with OI do not correlate with severities of final bone deformities.

Results

Conclusion