The 2q37-deletion syndrome: an update of the clinical spectrum including overweight, brachydactyly and behavioural features in 14 new patients.
The 2q37 locus is one of the most commonly deleted subtelomeric regions. Such a deletion has been identified in >100 patients by telomeric fluorescence in situ hybridization (FISH) analysis and, less frequently, by array-based comparative genomic hybridization (array-CGH). A recognizable '2q37-deletion syndrome' or Albright's hereditary osteodystrophy-like syndrome has been previously described. To better map the deletion and further refine this deletional syndrome, we formed a collaboration with the Association of French Language Cytogeneticists to collect 14 new intellectually deficient patients with a distal or interstitial 2q37 deletion characterized by FISH and array-CGH. Patients exhibited facial dysmorphism (13/14) and brachydactyly (10/14), associated with behavioural problems, autism or autism spectrum disorders of varying severity and overweight or obesity. The deletions in these 14 new patients measured from 2.6 to 8.8 Mb. Although the major role of HDAC4 has been demonstrated, the phenotypic involvement of several other genes in the deleted regions is unknown. We further refined the genotype-phenotype correlation for the 2q37 deletion. To do this, we examined the smallest overlapping deleted region for candidate genes for skeletal malformations (facial dysmorphism and brachydactyly), overweight, behavioural problems and seizures, using clinical data, a review of the literature, and the Manteia database. Among the candidate genes identified, we focus on the roles of PRLH, PER2, TWIST2, CAPN10, KIF1A, FARP2, D2HGDH and PDCD1.
CHU-Reims, HMB, Service de génétique, Reims, France.
Camille
C
Leroy
Emilie
E
Landais
Sylvain
S
Briault
Albert
A
David
Olivier
O
Tassy
Nicolas
N
Gruchy
Bruno
B
Delobel
Marie-José
MJ
Grégoire
Bruno
B
Leheup
Laurence
L
Taine
Didier
D
Lacombe
Marie-Ange
MA
Delrue
Annick
A
Toutain
Agathe
A
Paubel
Francine
F
Mugneret
Christel
C
Thauvin-Robinet
Stéphanie
S
Arpin
Cedric
C
Le Caignec
Philippe
P
Jonveaux
Mylène
M
Beri
Nathalie
N
Leporrier
Jacques
J
Motte
Caroline
C
Fiquet
Olivier
O
Brichet
Monique
M
Mozelle-Nivoix
Pascal
P
Sabouraud
Nathalie
N
Golovkine
Nathalie
N
Bednarek
Dominique
D
Gaillard
Martine
M
Doco-Fenzy
D000293:Adolescent; D000328:Adult; D001519:Behavior; D059327:Brachydactyly / Q000150:complications* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000150:complications* / Q000235:genetics*; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D005359:Fibrous Dysplasia, Polyostotic / Q000150:complications* / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D008607:Intellectual Disability / Q000150:complications* / Q000235:genetics*; D008297:Male; D050177:Overweight / Q000150:complications* / Q000235:genetics*; D055815:Young Adult