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Case Reports
. 2024 Jul;106(1):66-71.
doi: 10.1111/cge.14512. Epub 2024 Feb 28.

A founder variant expands the phenotype of WNT7B-related PDAC syndrome

Lama AlAbdi  1   2 , Zuhair Rahbeeni  3 , Sateesh Maddirevula  2 , Rana Helaby  2 , Firdous Abdulwahab  2 , Arif O Khan  4   5 , Lisa G Riley  6   7 , Amal Alhashem  8   9   10 , Nicolas Chassaing  11   12 , Robyn V Jamieson  13   14 , Fowzan S Alkuraya  2   8   9
Affiliations
Case Reports

A founder variant expands the phenotype of WNT7B-related PDAC syndrome

Lama AlAbdi et al. Clin Genet. 2024 Jul.

Abstract

Pulmonary hypoplasia, Diaphragmatic anomalies, Anophthalmia/microphthalmia, and Cardiac defects (PDAC) syndrome is a genetically heterogeneous multiple congenital malformation syndrome. Although pathogenic variants in RARB and STRA6 are established causes of PDAC, many PDAC cases remain unsolved at the molecular level. Recently, we proposed biallelic WNT7B variants as a novel etiology based on several families with typical features of PDAC syndrome albeit with variable expressivity. Here, we report three patients from two families that share a novel founder variant in WNT7B (c.739C > T; Arg247Trp). The phenotypic expression of this variant ranges from typical PDAC features to isolated genitourinary anomalies. Similar to previously reported PDAC-associated WNT7B variants, this variant was found to significantly impair WNT7B signaling activity further corroborating its proposed pathogenicity. This report adds further evidence to WNT7B-related PDAC and expands its variable expressivity.

Keywords: CAKUT; PDAC; founder; variable expressivity.

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References

REFERENCES

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