A large, ten-generation family with autosomal dominant preaxial polydactyly/triphalangeal thumb: Historical, clinical, genealogical, and molecular studies.

American journal of medical genetics. Part A 2023 Jan

filter terms:

We present a large, ten-generation family of 273 individuals with 84 people having preaxial polydactyly/triphalangeal thumb due to a pathogenic variant in the zone of polarizing activity regulatory sequence (ZRS) within the exon 5 of LMBR1. The causative change maps to position 396 of the ZRS, located at position c.423 + 4909C > T (chr7:156791480; hg38; LMBR1 ENST00000353442.10; rs606231153 NG_009240.2) in the intron 5 of LMBR1. The first affected individual with the disorder was traced back to mid-1700, when some settlers and workers established in Cervera de Buitrago, a small village about 82 km North to Madrid. Clinical and radiological studies of most of the affected members have been performed for 42 years (follow-up of the family by LFGA). Molecular studies have confirmed a pathogenic variant in the ZRS that segregates in this family. To the best of our knowledge, this is the largest family with preaxial polydactyly/triphalangeal thumb reported so far. © 2022 Wiley Periodicals LLC.

Citation

Luis Francisco González Álvarez, Jair Tenorio-Castaño, Fernando A Poletta, Fernando Santos-Simarro, Pedro Arias, Natalia Gallego, Iêda Maria Orioli, Stefan Mundlos, Eduardo E Castilla, Víctor Martínez-Glez, María Luisa Martínez-Frías, Víctor L Ruiz-Pérez, Julián Nevado, Pablo Lapunzina. A large, ten-generation family with autosomal dominant preaxial polydactyly/triphalangeal thumb: Historical, clinical, genealogical, and molecular studies. American journal of medical genetics. Part A. 2023 Jan;191(1):100-107