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1.  LINS, a modulator of the WNT signaling pathway, is involved in human cognition 
Background
Inherited intellectual disability (ID) conditions are a group of genetically heterogeneous disorders that lead to variable degrees of cognition deficits. It has been shown that inherited ID can be caused by mutations in over 100 different genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying the defective gene underlying an autosomal recessive ID in two sibs of an Emirati family.
Methods
A combined approach involving homozygosity mapping and whole-exome sequencing was used to identify the causative mutation. RNA analysis was performed to gain further insight into the pathogenic effect of the detected mutation.
Results
We have identified a homozygous splicing mutation (c.1219_1222+1delAAAGG) in the LINS gene in the affected children. LINS is the human homologue of the Drosophila segment polarity gene lin that encodes an essential regulator of the wingless/Wnt signaling. The identified mutation alters the first consensus nucleotide of the 5' donor splice junction of intron 5 and the 3' end of exon 5. Transcript analysis revealed that this change leads to an exon skipping event resulting in direct splicing of exon 4 to exon 6. Another mutation in LINS has been described very briefly in an Iranian family with autosomal recessive ID and microcephaly.
Conclusion
Our study confirms that LINS, a modulator of the WNT pathway, is an indispensable gene to human cognition and this finding sheds further light on the importance of WNT signaling in human brain development and/or function.
doi:10.1186/1750-1172-8-87
PMCID: PMC3847167  PMID: 23773660
2.  A mutation in KIF7 is responsible for the autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance 
Background
We previously reported the existence of a unique autosomal recessive syndrome consisting of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance mapping to chromosome 15q26.
Methods
In this manuscript, we have used whole exome sequencing on two affected members of a consanguineous family with this condition and carried out detailed bioinformatics analysis to elucidate the causative mutation.
Results
Our analysis resulted in the identification of a homozygous p.N1060S missense mutation in a highly conserved residue in KIF7, a regulator of Hedgehog signaling that has been recently found to be causing Joubert syndrome, fetal hydrolethalus and acrocallosal syndromes. The phenotype in our patients partially overlaps with the phenotypes associated with those syndromes but they also exhibit some distinctive features including multiple epiphyseal dysplasia.
Conclusions
We report the first missense homozygous disease-causing mutation in KIF7 and expand the clinical spectrum associated with mutations in this gene to include multiple epiphyseal dysplasia. The missense nature of the mutation might account for the unique presentation in our patients.
doi:10.1186/1750-1172-7-27
PMCID: PMC3492204  PMID: 22587682
KIF7; Acrocallosal; Joubert; Sonic hedgehog; Dysmorphism; Multiple epiphyseal dysplasia; Fetal hydrolethalus
3.  Molecular and clinical analysis of Ellis-van Creveld syndrome in the United Arab Emirates 
BMC Medical Genetics  2010;11:33.
Background
Ellis-van Creveld (EvC) syndrome is an autosomal recessive chondrodysplastic condition with clinical manifestations that include short-limbs and ribs, postaxial polydactyly and dysplastic nails and teeth. In about two thirds of patients, mutations in either EVC or EVC2 genes have been found to be the underlying cause.
Methods
In this paper, we describe the molecular (DNA sequencing) and clinical analysis of six children diagnosed with EvC from four different families from the United Arab Emirates (UAE).
Results
All the children had the common clinical and radiological features of this syndrome. However, DNA sequence analysis of the genes shown to be involved (EVC and EVC2) revealed a novel splice site mutation (c.2047-1G>T) in intron 13 of EVC2 gene in one family. In addition, we confirm previous mutational analyses that showed a truncating mutation in exon 13 of EVC gene (c.1813C>T; p.Q605X) in the second family and a single nucleotide deletion (c.981delG; p.K327fs) in exon 8 of EVC2 gene in the third family. No mutations in the exons, splice sites or the promoter regions of either gene have been found in the index case of the fourth family who exhibited "EvC-like" features.
Conclusions
Given the small population size of UAE, our data illustrates further the molecular heterogeneity observed in EvC patients and excludes the possibility of a common founder effect for this condition in the UAE reflecting the current ethnic diversity of the country.
doi:10.1186/1471-2350-11-33
PMCID: PMC2845574  PMID: 20184732

Results 1-3 (3)