Juvenile myoclonic epilepsy (JME) is characterized by seizures, severe cognitive abnormalities, and behavior impairments. These features could evolve over time and get worse, especially when the encephalopathy is pharmacoresistant. Thus, genetic studies should provide a better understanding of infantile epilepsy syndromes. Herein, we investigate the genetics of JME in a consanguineous family analyzing the copy number variations detected using over 700 K SNP arrays. We identified a 254-kb deletion in the 22q11.2 region, including only the TOP3B gene, detected in the patient and her father. TOP3B encodes a topoisomerase DNA (III) β protein and has been implicated in several neurological diseases such as schizophrenia and autism. In this study, we discuss the implication of the 22q11.2 region in neurodevelopmental disorders and the association of TOP3B with epilepsy.

Background Co‐occurrence of two genetic diseases is challenging for accurate diagnosis and genetic counseling. The recent availability of whole exome sequencing (WES) has dramatically improved the molecular diagnosis of rare genetic diseases in particular in consanguineous populations. Methods We report here on a consanguineous family from Southern Tunisia including three members affected with congenital ichthyosis. The index case had a hearing loss (HL) and ichthyosis and was primarily suspected as suffering from keratitis‐ichthyosis‐deafness (KID) syndrome. WES was performed for the index case, and all members of the nuclear family were sequenced (Sanger method). Results The WES approach allowed the identification of two strong candidate variants in two different genes; a missense mutation c.1334T>G (p.Leu445Trp) in exon 11 of SLC26A4 gene, associated with isolated HL and a novel missense mutation c.728G>T (p.Arg243Leu) in exon 8 of CYP4F22 gene likely responsible for ichthyosis. These two mutations were predicted to be pathogenic by three pathogenicity prediction softwares (Scale‐Invariant Feature Transform [SIFT], Polymorphism Phenotyping [PolyPhen], Mutation Taster) to underlie the HL and ichthyosis, respectively. Conclusions The present study raises awareness about the importance of familial history for accurate diagnosis of syndromic genetic diseases and differential diagnosis with co‐occurrence of two distinct clinical entities. In addition, in countries with limited resources, WES sequencing for a single individual provides a cost effective tool for molecular diagnosis confirmation and genetic counseling.

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Background Several studies have shown a high rate of consanguinity and endogamy in North African populations. As a result, the frequency of autosomal recessive diseases is relatively high in the region with the co‐occurrence of two or more diseases. Methods We report here on a consanguineous Libyan family whose child was initially diagnosed as presenting Fanconi anemia (FA) with uncommon skeletal deformities. The chromosome breakage test has been performed using mitomycin C (MMC) while molecular analysis was performed by a combined approach of linkage analysis and whole exome sequencing. Results Cytogenetic analyses showed that the karyotype of the female patient is 46,XY suggesting the diagnosis of a disorder of sex development (DSD). By looking at the genetic etiology of FA and DSD, we have identified p.[Arg798*];[Arg798*] mutation in FANCJ (OMIM #605882) gene responsible for FA and p.[Arg108*];[Arg1497Trp] in EFCAB6 (Gene #64800) gene responsible for DSD. In addition, we have incidentally discovered a novel mutation p.[Gly1372Arg];[Gly1372Arg] in the ERCC6 ( CSB ) (OMIM #609413) gene responsible for COFS that might explain the atypical severe skeletal deformities. Conclusion The co‐occurrence of clinical and overlapping genetic heterogeneous entities should be taken into consideration for better molecular and genetic counseling.