Whole-Exome Sequencing Identifies Mutated C12orf57 in Recessive Corpus Callosum Hypoplasia

Akizu, Naiara; Shembesh, Nuri; Ben‐Omran, Tawfeg; Bastaki, Lailá; Al-Tawari, Asma A.; Zaki, Maha S.; Koul, Roshan; Spencer, Emily; Rosti, Rasim Özgür; Scott, Eric; Nickerson, Elizabeth; Gabriel, Stacey; Gente, Gilberto da; Jiang, Li; Deardorff, Matthew A.; Conlin, Laura K.; Horton, Margaret A.; Zackai, Elaine H.; Sherr, Elliott H.; Gleeson, Joseph G.

doi:10.1016/j.ajhg.2013.02.004

Cited by 28 publications

(28 citation statements)

References 27 publications

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“…Zahrani et al [96] identified a homozygous mutation in the C12ORF57 gene (1A>G) in 4 siblings of Saudi Arabian origin with a similar phenotype. Akizu et al [97] identified the same mutation in 10 unrelated families of Arab decent, including the family reported by Li et al [95] , and a haplotype analysis indicated a founder effect.…”

Section: Agenesis Of Corpus-callosum-coloboma-mental Retardation (Temmentioning

confidence: 99%

“…Research teams worldwide are currently employing this technology to identify unknown genes causing dysmorphic syndromes including AR syndromes in consanguineous families [112] . Exome sequencing facilitated the identification of novel AR pathogenic genes in small consanguineous nuclear families [97] . The high rate of consanguinity in Arab countries coupled with the large family sizes will provide the material for exploring the still unknown AR genes causing dysmorphic syndromes.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

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Consanguinity and Dysmorphology in Arabs

Al‐Gazali

Hamamy²

2014

Hum Hered

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Incidence rates of congenital disorders among the 350 million inhabitants of Arab countries could be influenced via the people's demographic and cultural characteristics. Arabs usually marry at a young age and have large families. They share certain core cultural values and beliefs, with the family accepted as the central structure of society. Consanguineous marriage is favored and respected in most if not all Arab communities, and intrafamilial unions currently account for 20-50% of all marriages. First-cousin unions are especially popular and constitute almost one quarter of all marriages in many Arab countries. Consequently, autosomal recessive (AR) dysmorphic syndromes constitute a considerable proportion of all birth defects among Arabs. Arab geneticists, with their persistent commitment to advancing research, have contributed to the description of a number of rare and new AR syndromes with the identification of novel genes. The collaboration with research teams in high-income countries resulted in a plethora of data on pathogenic variants and their function in causing dysmorphic syndromes. There could still be a considerable number of rare dysmorphic syndromes that prevail among Arabs which are not hitherto described and whose underlying molecular pathologies are not yet defined. Arab countries should thus strive to deploy DNA diagnostics and to build research capability around local priorities. Furthermore, a characterization of the prevailing genetic disorders in each geographic location, together with their mutations, is needed to plan for appropriate screening and testing protocols. An overview of consanguinity in Arab countries and examples of dysmorphology syndromes associated with consanguinity with their available molecular bases will be discussed.

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Section: Agenesis Of Corpus-callosum-coloboma-mental Retardation (Temmentioning

confidence: 99%

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

Consanguinity and Dysmorphology in Arabs

Al‐Gazali

Hamamy²

2014

Hum Hered

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“…Exome sequencing studies identified homozygous and compound heterozygous mutations in C12orf57 to cause an autosomal recessive syndromic form of intellectual disability with ACC. C12orf57 is a highly conserved gene and is required for the development of the human corpus callosum [Akizu et al, 2013;Platzer et al, 2014].…”

Section: Discussionmentioning

confidence: 99%

Pre- and Postnatal Analysis of Chromosome 1q44 Deletion in Agenesis of Corpus Callosum

et al. 2015

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Agenesis of corpus callosum (ACC) is one of the common brain abnormalities and also a common finding in children with mental disability. ACC is heterogeneous and can occur as an isolated condition or as part of a syndrome. ACC can be accurately identified by the absence of the cavum septum pallucidum and tear drop effect of the lateral ventricle after 18 weeks of pregnancy in an ultrasound scan. Genetic causes have been attributed to 30-45% of cases with ACC. Submicroscopic deletions of 1q43q44 have been reported in several cases of ACC. The AKT3 gene, mapped to 1q44, is required for the development of the callosum and brain size. It is considered to be a candidate gene for ACC. We studied a total of 22 cases with ACC, in pre- and postnatal samples using FISH probes. None of the samples showed a deletion in 1q44, implying that the AKT3 gene may not be associated with ACC.

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“…More recently, the phenotype of patients with FLNA related PVNH has been expanded to include a wide spectrum of connective tissue and vascular anomalies, including aortic root dilatation 45,46 . Autosomal recessive forms of PVNH have been described in patients with mutations in ARFGEF2 29 and C12orf57 47,48 . Other potential genetic loci for genes associated with PVNH include 7q11.23, 5p15.1, 5p15.33, 5q14.3-q15 and 4p15 49 .…”

Section: Recent Advances In Genetics and Pathomechanism Of MCDmentioning

confidence: 99%

Genomic Variants and Variations in Malformations of Cortical Development

Jamuar

Walsh

2015

Pediatric Clinics of North America

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Malformations of cortical development (MCD) are a common cause of neurodevelopmental delay and epilepsy and are caused by disruptions in the normal development of the cerebral cortex. Advances in genetic tools have expanded our understanding of the genetics of these malformations over the past few years, with a number of new causative genes identified in patients with MCD. In addition, there has been a vast expansion in the phenotypic characterization of the known genes, with a wide range as well as severity of malformations being reported. There is increasing evidence of role of de novo mutations, including those occurring post fertilization, in MCD. These “somatic” mutations may not be detectable by traditional methods of genetic testing performed on blood DNA. Identification of the genetic etiology can help in guiding families in future pregnancies. Recent work has highlighted how elucidation of key molecular pathway can also allow for targeted therapeutic interventions.

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Whole-Exome Sequencing Identifies Mutated C12orf57 in Recessive Corpus Callosum Hypoplasia

Cited by 28 publications

References 27 publications

Consanguinity and Dysmorphology in Arabs

Consanguinity and Dysmorphology in Arabs

Pre- and Postnatal Analysis of Chromosome 1q44 Deletion in Agenesis of Corpus Callosum

Genomic Variants and Variations in Malformations of Cortical Development

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