Molecular characterization of 1q44 microdeletion in 11 patients reveals three candidate genes for intellectual disability and seizures.
Patients with a submicroscopic deletion at 1q43q44 present with intellectual disability (ID), microcephaly, craniofacial anomalies, seizures, limb anomalies, and corpus callosum abnormalities. However, the precise relationship between most of deleted genes and the clinical features in these patients still remains unclear. We studied 11 unrelated patients with 1q44 microdeletion. We showed that the deletions occurred de novo in all patients for whom both parents' DNA was available (10/11). All patients presented with moderate to severe ID, seizures and non-specific craniofacial anomalies. By oligoarray-based comparative genomic hybridization (aCGH) covering the 1q44 region at a high resolution, we obtained a critical deleted region containing two coding genes-HNRNPU and FAM36A-and one non-coding gene-NCRNA00201. All three genes were expressed in different normal human tissues, including in human brain, with highest expression levels in the cerebellum. Mutational screening of the HNRNPU and FAM36A genes in 191 patients with unexplained isolated ID did not reveal any deleterious mutations while the NCRNA00201 non-coding gene was not analyzed. Nine of the 11 patients did not present with microcephaly or corpus callosum abnormalities and carried a small deletion containing HNRNPU, FAM36A, and NCRNA00201 but not AKT3 and ZNF238, two centromeric genes. These results suggest that HNRNPU, FAM36A, and NCRNA00201 are not major genes for microcephaly and corpus callosum abnormalities but are good candidates for ID and seizures.
CHU Nantes, Service de Génétique Médicale, Nantes, France.
Gaelle
G
Thierry
Claire
C
Bénéteau
Olivier
O
Pichon
Elisabeth
E
Flori
Bertrand
B
Isidor
Françoise
F
Popelard
Marie-Ange
MA
Delrue
Laetitia
L
Duboscq-Bidot
Ann-Charlotte
AC
Thuresson
Bregje W M
BW
van Bon
Dorothée
D
Cailley
Caroline
C
Rooryck
Agathe
A
Paubel
Corinne
C
Metay
Anne
A
Dusser
Laurent
L
Pasquier
Mylène
M
Béri
Céline
C
Bonnet
Sylvie
S
Jaillard
Christèle
C
Dubourg
Bassim
B
Tou
Marie-Pierre
MP
Quéré
Cecilia
C
Soussi-Zander
Annick
A
Toutain
Didier
D
Lacombe
Benoit
B
Arveiler
Bert B A
BB
de Vries
Philippe
P
Jonveaux
Albert
A
David
Cédric
C
Le Caignec
D002675:Child, Preschool; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D055028:Comparative Genomic Hybridization; D019066:Facies; D005260:Female; D020869:Gene Expression Profiling; D034722:Heterogeneous-Nuclear Ribonucleoprotein U / Q000235:genetics*; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D009154:Mutation; D022661:RNA, Untranslated / Q000235:genetics*; D012640:Seizures / Q000235:genetics*
D034722:Heterogeneous-Nuclear Ribonucleoprotein U; D022661:RNA, Untranslated