case_images: PMC9393300_01
case_images: (A) Family pedigree. Squares represent men, circles women, black symbols affected family members, white symbols unaffected members, grey symbols members not evaluated; the asterisk identifies subjects carrying the WNT1 p. Leu370Val variant. The arrow identifies the proband. (B) Representative Sanger sequencing results of a healthy subject and the proband: the sequencing chromatogram of the index patient indicates a heterozygous WNT1 c.1108C>G mutation (nomenclature according to National Center for Biotechnology Information Reference Sequence: NM_005430). (C) Alignment of Wnt1 protein in different vertebrate species. The highly conserved last amino acid (L) of Wnt1 is highlighted in the box.
case_images: fendo-13-918682-g001.jpg
case_images: PMC9393300_01_fendo-13-918682-g001.jpg
case_images: f1
case_images: The proband, a 35 year -old Caucasian woman ( Figure 1 , II.2), was referred to our outpatient clinic in June 2019 for evaluation of early-onset osteoporosis. All family members ( Figure 1 ) were in good health except the younger sister ( Figure 1 , II.6) who had a congenital myopathy associated with an unspecified cardiopathy. After filtering, one candidate heterozygous missense variant, c.1108C>G (p.Leu370Val) (rs897040674 dbSNP), in the WNT1 gene (NM_005430) was found ( Figure 1 ). Finally, by investigating her relatives by Sanger, the same genetic alteration was found both in the proband father ( Figure 1 , I.1) and in the older brother ( Figure 1 , II.1), while its presence in the mother, both sisters and the younger brother was excluded.
case_images: (A) Magnetic resonance imaging of the lumbar spine revealing the presence of vertebral fractures of T12 and L1. Peri-lesion edema of both vertebrae indicating recent fractures is shown (arrows). (B) X-ray of the thoracic spine shows vertebral fractures from T6 to T9.
case_images: fendo-13-918682-g002.jpg
case_images: PMC9393300_01_fendo-13-918682-g002.jpg
case_images: f2
case_images: Moreover, the MRI signal suggested the presence of peri-lesion edema, as it was hypointense in T1 and hyperintense in STIR sequences indicating the recent nature of the vertebral fractures ( Figure 2 ). In January 2019, X-ray of the whole spine showed additional vertebral fractures from T6 to T9 ( Figure 2 ).