Pseudoautosomal inheritance of Léri-Weill syndrome: what does it mean?
The short stature homeobox (SHOX) gene is located in the pseudoautosomal region 1 of both sex chromosomes. Haploinsufficiency of SHOX leads to different phenotypes ranging from isolated short stature to Léri-Weill syndrome characterized by short stature, mesomelia and Madelung deformity. We describe a family with a SHOX deletion originally located on the Y chromosome and transmitted from father to daughter by crossover during meiosis. The male index patient presented with short stature, mesomelia and mild Madelung deformity. His father had a normal height but slightly disproportionate short legs. The sister of the index patient presented with marked Madelung deformity and normal height. A deletion of the SHOX gene was identified in the male index patient, his father and his sister. Metaphase fluorescence in situ hybridization (FISH) analyses showed a deletion of the SHOX gene on the Y chromosomes of the index patient and his father, and on the X chromosome of his sister, indicating that a meiotic crossover of the SHOX gene region between the X and Y chromosomes had occurred. The pseudoautosomal region 1 is a known recombination 'hot spot' in male meiosis. Published genetic maps indicate high recombination frequency of ∼40% for SHOX in male meiosis leading to pseudoautosomal inheritance.
Evers
C
C
Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.
Heidemann
P H
PH
Dunstheimer
D
D
Schulze
E
E
Haag
C
C
Janssen
J W G
JW
Fischer
C
C
Jauch
A
A
Moog
U
U
D002675:Child, Preschool; D025063:Chromosome Disorders / Q000235:genetics*; D005260:Female; D006130:Growth Disorders / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D010009:Osteochondrodysplasias / Q000235:genetics; D010375:Pedigree; D000074122:Short Stature Homeobox Protein
D018398:Homeodomain Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein