High bone mass due to novel LRP5 and AMER1 mutations

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Costantini , A , Kekalainen , P , Makitie , R E & Makitie , O 2017 , ' High bone mass due to novel LRP5 and AMER1 mutations ' , European Journal of Medical Genetics , vol. 60 , no. 12 , pp. 675-679 . https://doi.org/10.1016/j.ejmg.2017.09.001

Title: High bone mass due to novel LRP5 and AMER1 mutations
Author: Costantini, Alice; Kekalainen, Paivi; Makitie, Riikka E.; Makitie, Outi
Contributor organization: Clinicum
Children's Hospital
Lastentautien yksikkö
HUS Children and Adolescents
HUS Internal Medicine and Rehabilitation
Date: 2017-12
Language: eng
Number of pages: 5
Belongs to series: European Journal of Medical Genetics
ISSN: 1769-7212
DOI: https://doi.org/10.1016/j.ejmg.2017.09.001
URI: http://hdl.handle.net/10138/298168
Abstract: WNT signaling is a key regulator of bone metabolism and its increased or decreased activity leads to skeletal disorders. Here we describe two patients with high bone mass (HBM) caused by novel mutations in two different WNT pathway components. The first patient is a 53-year-old male with HBM. He was diagnosed at adult age based on significantly increased bone mineral density (BMD). He has undergone several surgeries due to excessive bone in ear canals, bilateral jaw exostoses and mandibular tori. Radiographs show severe cortical thickening of cranial and long bones. Sanger sequencing identified a novel heterozygous mutation c. 592A> T (p. N198Y) in LRP5 (Low-density lipoprotein receptor-related protein 5). The second patient, an adolescent female, was diagnosed with skeletal dysplasia in early childhood. She had macrocephaly (head circumference +6.0 SD), facial dysmorphism, delayed motor development, laryngomalasia and epilepsy. Radiographic findings were consistent with osteopathia striata with cranial sclerosis. A novel heterozygous frameshift mutation c. 655del (p. E219Rfs* 63) in AMER1 (APC Membrane Recruiting Protein 1) was identified. Although both mutations are predicted to lead to increased WNT signaling with a consequent increase in bone formation, the resulting phenotypes are different; cranial sclerosis versus macrocephaly, long bone cortical thickening versus vertical striations and discordant neurological development. This report underscores the diversity of genotypes and phenotypes of HBM and facilitates their differential diagnosis. (C) 2017 Elsevier Masson SAS. All rights reserved.
Subject: High bone mass
Osteopathia striata
WNT signaling
3111 Biomedicine
1184 Genetics, developmental biology, physiology
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion

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