Malignant peripheral nerve sheath tumor in a patient with Werner's syndrome

Rosa, Maria Angela La; Falcone, Giuseppe; Santis, V. De; Azzaro, O.

doi:10.1007/bf02637324

Cited by 1 publication

(1 citation statement)

References 9 publications

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“…Mutations of other members of this family are seen in Bloom's syndrome and Rothmund–Thomson's syndrome, all of which are characterized by increased genomic instability and increased cancer predisposition (Sharma et al, 2020). While the association of Werner's syndrome with elevated risk of malignant tumors is widely reported in the literature, it is often associated with thyroid neoplasms, melanoma, and bone and soft tissue sarcomas, and only four cases of MPNST have been reported in the literature so far (Goto et al, 1996; Rosa et al, 2003). MPNST is extremely rare, but devastating tumor that originates in the nerve sheath with a 5‐year survival of 35%–60% (Ducatman et al, 1986; Stucky et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Early‐onset diabetes mellitus as a presenting feature of Werner's syndrome in an Indian family

Hoff,

Xing,

Simha

et al. 2023

Molec Gen & Gen Med

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BackgroundDiabetes mellitus (DM) in children and adolescents is typically caused by type 1 DM, followed by type 2 DM and maturity‐onset diabetes of the young (MODY). We report an unusual Asian Indian family in which three members presented with DM at ages 15, 20, and 30, but not fitting the typical clinical picture of type 1 DM, type 2 DM, or MODY. The primary objective was to elucidate the molecular genetic basis of DM in this family.MethodsThe proband, a 22‐year‐old man, had short stature, gray hair, osteoporosis, and markedly reduced subcutaneous fat on the body, especially on the extremities along with acanthosis nigricans, and developed myxoid malignant peripheral nerve sheath tumor. Detailed family history revealed multiple loops of consanguinity. The proband underwent whole‐genome sequencing, and seven relatives underwent whole‐exome sequencing.ResultsThe proband and three additional family members were found to have the homozygous c.561A>G nucleotide variant of WRN RecQ‐like helicase (WRN) gene consistent with the diagnosis of Werner's syndrome. The c.561A>G variant induces a new splicing site on exon 6 resulting in a truncated WRN protein, p.Lys187Trpfs*13.ConclusionOur report brings to attention the onset of DM during childhood or early adulthood in patients with Werner's syndrome who typically develop type 2 DM around the age of 30–40 years. Presence of consanguinity among parents, dysmorphic features, and malignancy should prompt consideration of diagnosis of Werner's syndrome.

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