Further delineation of the 17p13.3 microdeletion involving YWHAE but distal to PAFAH1B1: four additional patients.
BACKGROUND
The 17p13.3 deletion syndrome (or Miller-Dieker syndrome, MDS, MIM 247200) is characterized by lissencephaly, mental retardation and facial dysmorphism. The phenotype is attributed to haploinsufficiency of two genes present in the minimal critical region of MDS: PAFAH1B1 (formerly referred to as LIS1) and YWHAE. Whereas isolated PAFAH1B1 deletion causes lissencephaly, YWHAE is a candidate for the dysmorphic phenotype associated with MDS.


OBJECTIVE
We describe clinical, neuroradiological and molecular data in four patients with a 17p13.3 deletion distal to PAFAH1B1 involving YWHAE.


RESULTS
All patients presented with mild or moderate developmental delay and pre and/or post-natal growth retardation. Patients A, B and C had neuro-imaging anomalies: leucoencephalopathy with macrocephaly (patients A and C), Chiari type 1 malformation (patient A) and paraventricular cysts (patient C). Patient B had patent ductus arteriosus and pulmonary arterial hypertension. Patient C had unilateral club foot. Patient D had enlarged Virchow Robin spaces, microcornea, and chorioretinal and lens coloboma. Array-CGH revealed de novo terminal 17p13.3 deletions for patient A and B, and showed interstitial 17p13.3 deletions of 1.4 Mb for patient C and of 0.5 Mb for patient D. In all patients, PAFAH1B1 was not deleted.


CONCLUSIONS
Our patients confirm that 17p deletion distal to PAFAH1B1 have a distinctive phenotype : mild mental retardation, moderate to severe growth restriction, white matter abnormalities and developmental defects including Chiari type 1 malformation and coloboma. Our patients contribute to the delineation and clinical characterization of 17p13.3 deletion distal to PAFAH1B1 and highlight the role of the region containing YWHAE in brain and eye development and in somatic growth.
Schiff
Manuel
M
Department of Pediatric Neurology & Metabolic Diseases, APHP-Robert DEBRE University Hospital, Paris, France.
Delahaye
Andrée
A
Andrieux
Joris
J
Sanlaville
Damien
D
Vincent-Delorme
Catherine
C
Aboura
Azzedine
A
Benzacken
Brigitte
B
Bouquillon
Sonia
S
Elmaleh-Berges
Monique
M
Labalme
Audrey
A
Passemard
Sandrine
S
Perrin
Laurence
L
Manouvrier-Hanu
Sylvie
S
Edery
Patrick
P
Verloes
Alain
A
Drunat
Séverine
S
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics* / Q000378:metabolism; D048948:14-3-3 Proteins / Q000235:genetics* / Q000378:metabolism; D000015:Abnormalities, Multiple / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics* / Q000378:metabolism; D054221:Classical Lissencephalies and Subcortical Band Heterotopias / Q000235:genetics*; D005260:Female; D057895:Haploinsufficiency; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
D048948:14-3-3 Proteins; D008869:Microtubule-Associated Proteins; C482983:YWHAE protein, human; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human