Further delineation of novel 1p36 rearrangements by array-CGH analysis: narrowing the breakpoints and clarifying the "extended" phenotype.

High resolution oligonucleotide array Comparative Genome Hybridization technology (array-CGH) has greatly assisted the recognition of the 1p36 contiguous gene deletion syndrome. The 1p36 deletion syndrome is considered to be one of the most common subtelomeric microdeletion syndromes and has an incidence of ~1 in 5000 live births, while respectively the "pure" 1p36 microduplication has not been reported so far. We present seven new patients who were referred for genetic evaluation due to Developmental Delay (DD), Mental Retardation (MR), and distinct dysmorphic features. They all had a wide phenotypic spectrum. In all cases previous standard karyotypes were negative. Array-CGH analysis revealed five patients with interstitial 1p36 microdeletion (four de novo and one maternal) and two patients with de novo reciprocal duplication of different sizes. These were the first reported "pure" 1p36 microduplication cases so far. Three of our patients carrying the 1p36 microdeletion syndrome were also found to have additional pathogenetic aberrations. These findings (del 3q27.1; del 4q21.22-q22.1; del 16p13.3; dup 21q21.2-q21.3; del Xp22.12) might contribute to the patients' severe phenotype, acting as additional modifiers of their clinical manifestations. We review and compare the clinical and array-CGH findings of our patients to previously reported cases with the aim of clearly delineating more accurate genotype-phenotype correlations for the 1p36 syndrome that could allow for a more precise prognosis.

Giannikou K ，Fryssira H ，Oikonomakis V ，Syrmou A ，Kosma K ，Tzetis M ，Kitsiou-Tzeli S ，Kanavakis E ... -  《-》

Further delineation of deletion 1p36 syndrome in 60 patients: a recognizable phenotype and common cause of developmental delay and mental retardation.

Battaglia A ，Hoyme HE ，Dallapiccola B ，Zackai E ，Hudgins L ，McDonald-McGinn D ，Bahi-Buisson N ，Romano C ，Williams CA ，Brailey LL ，Zuberi SM ，Carey JC ... -  《-》

Microdeletion and microduplication 17q21.31 plus an additional CNV, in patients with intellectual disability, identified by array-CGH.

The recognition of the 17q21.31 microdeletion and microduplication syndrome has been facilitated by high resolution oligonucleotide array comparative genome hybridization technology (aCGH). Molecular analysis of the 17q21.31 microdeletion/duplication syndrome demonstrated a critical region involving at least six genes, including STH and MAPT. The 17q21.31 microdeletion syndrome has an incidence of 1 in 16,000 births, while the microduplication 17q21.31 has been reported so far in only five patients. In general, phenotypes associated with 17q21.31 microduplication seem to be milder than those associated with the microdeletion. Here, we present four patients who have been referred for genetic evaluation by clinical geneticists due to developmental delay and minor congenital abnormalities. Previous standard karyotypes were negative, while aCGH analysis revealed three patients with 17q21.31 microdeletion and one with the respective microduplication, being the sixth reported case so far. Most importantly one of the microdeletion cases involves only partial MAPT gene deletion while leaving the STH gene intact. Two of our patients, one with the 17q21.31 microdeletion and another with the respective microduplication, carried additional clinically relevant microdeletions (del Xq21.31 and del 15q11.2, respectively), possibly modifying their phenotype.

Kitsiou-Tzeli S ，Frysira H ，Giannikou K ，Syrmou A ，Kosma K ，Kakourou G ，Leze E ，Sofocleous C ，Kanavakis E ，Tzetis M ... -  《-》

Microdeletion at chromosome 4q21 defines a new emerging syndrome with marked growth restriction, mental retardation and absent or severely delayed speech.

Bonnet C ，Andrieux J ，Béri-Dexheimer M ，Leheup B ，Boute O ，Manouvrier S ，Delobel B ，Copin H ，Receveur A ，Mathieu M ，Thiriez G ，Le Caignec C ，David A ，de Blois MC ，Malan V ，Philippe A ，Cormier-Daire V ，Colleaux L ，Flori E ，Dollfus H ，Pelletier V ，Thauvin-Robinet C ，Masurel-Paulet A ，Faivre L ，Tardieu M ，Bahi-Buisson N ，Callier P ，Mugneret F ，Edery P ，Jonveaux P ，Sanlaville D ... -  《-》

De novo unbalanced translocation 2;4 characterized by metaphase CGH and array CGH in a child with mental retardation and dysmorphic features.

It is known from postnatal diagnosis that imbalances of the subtelomeric regions contribute significantly to idiopathic mental retardation. We report a case of a 4-year-old child with growth retardation, minor physical abnormalities, hypotonia and developmental delay associated with a derivative chromosome 4. Molecular cytogenetic investigations were performed to characterize the chromosomal rearrangement. Multi fluorescence in situ hybridization revealed the presence of chromosome 2 material on the derivative chromosome 4. Metaphase comparative genomic hybridization detected a terminal 4q34 deletion. Array CGH analysis could precise breakpoints with duplication 2q36 → qter. The clinical phenotype was similar to those described in cases with a trisomy 2qter. This study emphasizes the value of array CGH to detect or characterize chromosome rearrangements in mentally retarded patients. Unlike metaphase CGH, the high resolution of array CGH in subtelomeric regions allows an accurate description of chromosomal aberrations.

Debost-Legrand A ，Capri Y ，Gouas L ，Pebrel-Richard C ，Veronese L ，Tchirkov A ，Haoud K ，Boespflug-Tanguy O ，Goumy C ，Vago P ... -  《-》