The 12q14 microdeletion syndrome: six new cases confirming the role of HMGA2 in growth.
We report six patients with array deletions encompassing 12q14. Out of a total of 2538 array investigations carried out on children with developmental delay and dysmorphism in three diagnostic testing centres, six positive cases yielded a frequency of 1 in 423 for this deletion syndrome. The deleted region in each of the six cases overlaps significantly with previously reported cases with microdeletions of this region. The chromosomal range of the deletions extends from 12q13.3q15. In the current study, we report overlapping deletions of variable extent and size but primarily comprising chromosomal bands 12q13.3q14.1. Four of the six deletions were confirmed as de novo events. Two cases had deletions that included HMGA2, and both children had significant short stature. Neither case had osteopoikilosis despite both being deleted for LEMD3. Four cases had deletions that ended proximal to HMGA2 and all of these had much better growth. Five cases had congenital heart defects, including two with atrial septal defects, one each with pulmonary stenosis, sub-aortic stenosis and a patent ductus. Four cases had moderate delay, two had severe developmental delay and a further two had a diagnosis of autism. All six cases had significant speech delay with subtle facial dysmorphism.
National Centre for Medical Genetics, Our Lady's Childrens Hospital, Dublin, Ireland. Sallyann.lynch@olchc.ie
Sally Ann
SA
Lynch
Nicola
N
Foulds
Ann-Charlotte
AC
Thuresson
Amanda L
AL
Collins
Göran
G
Annerén
Bernt-Oves
BO
Hedberg
Carol A
CA
Delaney
James
J
Iremonger
Caroline M
CM
Murray
John A
JA
Crolla
Colm
C
Costigan
Wayne
W
Lam
David R
DR
Fitzpatrick
Regina
R
Regan
Sean
S
Ennis
Freddie
F
Sharkey
D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D001827:Body Height; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D004392:Dwarfism / Q000235:genetics; D005260:Female; D025743:HMGA2 Protein / Q000235:genetics*; D006801:Humans; D008297:Male; D056730:Silver-Russell Syndrome / Q000235:genetics; D013577:Syndrome
D025743:HMGA2 Protein
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