PMC9393300_01
(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.
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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.
(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.
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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 ).