Novel findings, mini-review and dysmorphological characterization of 16p13.11 microduplication syndrome.

The short arm of chromosome 16 and especially the region 16p13.11 is a chromosome region where many structural variants, especially deletions and duplications, can be observed. Although deletions of this region are clinically well defined, duplications are rare, and so far, there is no established clinical consensus in regard with its clinical picture, and especially the dysmorphic perspective of the disease is far from being clear. A 5-year-and-2-month-old patient who presented with epilepsy, autism and late speech onset complaints was evaluated in our genetics department. On physical examination, unilateral preauricular skin tag and upslanting palpebral fissures were noted. Microarray analysis was performed and reported as ([hg19]: 16p13.11 (14.897.804-16.730.375) x3). The literature review revealed only a few reports about the syndrome, but some dysmorphological findings appear to recur in different reports, which enables a possible characterization. Dysmorphic findings were discussed.

Interchromosomal effect: Report of a father and son, bearing different translocations of the same chromosome, and a review of the current literature.

Interchromosomal effect is a controversial phenomenon postulating that during gametogenesis of translocation carriers, aside from the unbalanced segregation of chromosomes involved in the translocation, other, structurally normal chromosomes might also be affected and segregated abnormally. Here, we present a balanced reciprocal translocation carrier t(15;20)(q11;p13), and his son, bearing a different translocation of chromosome 15, t(15;Y)(q11;q12). To further elucidate the so-far-controversial interchromosomal effect phenomenon, published original articles and case reports about interchromosomal effect were reviewed. The father was a carrier of t(15;20)(q11;p13). His wife's karyotype was normal. During a pregnancy occurred without any preceding procedure, amniocentesis was recommended to the family and performed. Result of the amniocentesis revealed a different translocation of chromosome 15; t(15;Y)(q11;q12). To our knowledge, this is the first report of two generations within a family, bearing different translocations of a chromosome. On top of all previous studies investigating ICE, our case adds an important finding, showing not only the rate of aneuploidies of structurally normal chromosomes, but also the rate of this 'alternating translocations' might be increased in translocation carriers, and this could be an important clue about interchromosomal effects.

A Novel Pathogenic Variant of the CFTR Gene in a Patient with Cystic Fibrosis Phenotype-c.4096A > T.

Cystic fibrosis is a chronic multisystemic disease originating from functional alterations in CFTR (cystic fibrosis transmembrane conductance regulator) protein. To date, more than 300 pathogenic variants have been described in the literature. However, the diagnosis of CF, which was thought to become easier after the CFTR gene was identified, became more complicated due to the enormous amount of variations. In this study, we present a patient whose clinical findings were consistent with cystic fibrosis (CF) and showed a homozygous missense change that is not previously reported in the CFTR gene as pathogenic. In the next-generation sequencing analysis, homozygous c.4096A > T single-nucleotide exchange (I1366F [p.Ile1366Phe], missense) was shown in both alleles of the patient' CFTR gene. According to our database analysis, this variant has not yet been previously reported (VarSome, ClinVar, MutationTaster, Ensembl, dbSNP, PubMed). We do consider the change as pathogenic since the patient's findings were compatible with CF and the data analysis was in favor of pathogenicity. The most recent consensus report published in 2017 emphasized the importance of CFTR gene analysis, and this study emphasizes the difficulties of associating CFTR gene variations with a clinical picture and constitutes a new data on the genotype-phenotype correlation of CFTR variants. Also, considering the frequency of CF (according to World Health Organization data, every 1 out of 2,000-3,000 infants is born with CF in European Union countries and every 1 out of 3,500 in the United States) as well as the increasing rate of molecular studies performed on CF patients worldwide, reporting novel variation has an additional value.