3p14 deletion is a rare contiguous gene syndrome: report of 2 new patients and an overview of 14 patients.

Interstitial deletions of chromosome 3p14p12 are a rare chromosome rearrangement. Twenty-six patients have been reported in the literature to date, however, a specific clinical phenotype has not yet been delineated. We describe three patients (two new) with overlapping chromosome 3p14p12 deletions and review the clinical and molecular data of 11 well-characterized, published cases. These patients had a number of features in common, such as short stature, failure to thrive, facial dysmorphism, congenital heart defects, urogenital abnormalities, neurological problems, hearing loss, and global developmental delay, suggesting that the interstitial chromosome 3p14p12 deletion gives rise to a multiple congenital anomaly syndrome. Some of the patients show clinical overlap with other complex syndromes such as CHARGE syndrome. Genotype-phenotype analysis revealed candidate genes for parts of the clinical features suggesting that the 3p14 deletion is a contiguous gene syndrome.

Distal limb deficiencies, micrognathia syndrome, and syndromic forms of split hand foot malformation (SHFM) are caused by chromosome 10q genomic rearrangements.

BACKGROUND: The 10q24 chromosomal region has previously been implicated in split hand foot malformation (SHFM). SHFM3 was mapped to a large interval on chromosome 10q. The corresponding dactylaplasia mouse model was linked to the syntenic locus on chromosome 19. It was shown that the two existing Dac alleles result from MusD-insertions upstream of or within Dactylin (Fbxw4). However, all efforts to find the underlying cause for the human SHFM3 have failed on the analysis of all the genes within the linkage region. Intriguingly a submicroscopic duplication within the critical locus on chromosome 10q24 was associated with the phenotype. METHODS AND RESULTS: As a part of screening for genomic rearrangements in cases with unexplained syndromic limb defects, a cohort of patients was analysed by array comparative genomic hybridisation (CGH). A 10q24 microduplication was detected in two individuals with distal limb deficiencies associated with micrognathia, hearing problems and renal hypoplasia. In addition, in a family with two affected siblings, a somatic/gonadal mosaicism for the microduplication was detected in the apparently healthy mother. Using a high resolution oligoarray further delineation of the duplication size was performed. CONCLUSIONS: The detected 10q24 genomic imbalance in our syndromic patients has a similar size to the duplication in the previously reported individuals with an isolated form of SHFM, thus extending the clinical spectrum of SHFM3. These findings clearly demonstrate the importance of array CGH in the detection of the aetiology of complex, clinically heterogeneous entities.