New candidate region for mirror hand movements: two patients with terminal 9p deletion and 20p duplication.

The 9p deletion syndrome, which was defined in a detailed way in the previous studies, was characterized by various clinical features such as psychomotor retardation, dysmorphic features and genital anomalies. In contrast to 9p deletion syndrome, 20p duplication was rarely reported in the literature with only a few case reports. Regarding the combination of 9p deletion syndrome and 20p duplication, we found that it was reported in only four patients. In the current study, we aimed to investigate a rare chromosomal rearrangement, partial monosomy 9p and trisomy 20p which was observed in two patients with mirror hand movements. The mirror hand movements was influenced by the combination of genetic and environmental factors. While some cases have been associated with mutations in the DCC, NTN1, RAD51, and DNAL4, there were many cases where the genetic basis of mirror hand movements remained unexplained. There was no alteration detected in genes that were previously known as a cause of mirror hand movement in our patients. This new finding could potentially be attributed to the dosage effect of genes within the 9p deletion or 20p duplication regions or to the genes disrupted within the breakpoint region. Future research focusing on the genes within this genomic locus may hold the potential to uncover novel etiologic reasons for mirror hand movements.

Acrocapitofemoral dysplasia: Novel mutation in IHH in two adult patients from the third family in the literature and progression of the disease.

Acrocapitofemoral dysplasia (ACFD) is a rare autosomal recessive skeletal dysplasia characterized by short stature with short limb dwarfism, brachydactyly, and a narrow thorax. Major radiographic features are egg-shaped capital femoral epiphyses with a short femoral neck and cone-shaped epiphyses, mainly in the hands and hips. To date, only four child patients from two families have been reported. We describe two adult patients with ACFD with a novel homozygous c.478C>T (p.Arg160Cys) mutation in IHH in the third family of the literature. The reported cases showed a middle phalanges which fused with distal phalanges in the fifth toes, the typical configuration of metacarpals, radial angulation and extremely short femoral neck. These findings could help the diagnosis of ACFD in adult patients. We hope that this new family will be a helpful guide for predicting and managing the prognosis of diagnosed children.

Goldberg-Shprintzen Syndrome Associated with a Novel Variant in the KIFBP Gene.

Goldberg-Shprintzen syndrome (GOSHS) is characterized by microcephaly, developmental delay, dysmorphic features, Hirschsprung disease (HSCR), and brain anomalies. The kinesin family binding protein (KIFBP; MIM 60937) gene has been identified as the responsible gene of the syndrome. To date, 16 different biallelic KIFBP mutations have been identified in 34 patients with GOSHS. Even though most of these mutations are nonsense and frameshift, 3 missense mutations have also been described. Here, we report an 18-month-old patient with microcephaly, developmental delay, dysmorphic features and HSCR. Exome analysis was performed to clarify the etiology of the clinical features. A previously unreported homozygous c.1723delC (p.H575Ifs*19) variant was detected in the last exon 7 of KIFBP which led to GOSHS. According to our findings, we suggest that this mutation expands mutational databases and contributes to the understanding of the phenotypic features of the syndrome.

Analysis of rearrangements of the CFTR gene in patients from Turkey with CFTR-related disorders: frequent exon 2 deletion.

Cystic fibrosis is a hereditary disease that mostly affects the sweat glands, respiratory system, digestive system, and reproductive system. Many and various types of mutations have been reported in CFTR in different ethnicities and countries/regions. Analysis of CFTR gene rearrangements is recommended in patients with unidentified mutated alleles in CFTR sequencing analysis. We collected MLPA analyses of 527 patients from Turkey who had at least one unidentified mutation in CFTR sequence analysis. Heterozygous/homozygous deletions were detected in the CFTR gene in 49 individuals (9.2%) from 35 families. Twelve different single/multi exon deletions were demonstrated, two of which were not previously reported in the literature. Mutations have previously reported in patients from various regions including Asia, Europe, and Africa, and Turkey is located at a crossroads between them. The most frequent mutation was the exon 2 deletion, accounting for 60%. Moreover, patients with exon 2 deletions, were especially originated from northern Turkey. This finding is valuable in leading and shaping planned screening programs in Turkey. Our study, the most comprehensive study for rearrangement analysis in patients from Tukey, revealed a candidate hotspot region of patients suspected of having CFTR-related disorders from Turkey.

A Case of Ataxia-telangiectasia Presented With Hemophagocytic Syndrome.

Ataxia-telangiectasia (A-T) is a multisystem disease caused by a genetic defect located on the long arm of chromosome 11 (11p22-23). The gene defect results in the loss of A-T-mutated protein, subsequently leading to unrepaired DNA fractures and defects in the signal transduction pathway. As a result, characteristic findings arise, including recurrent sinopulmonary infections, hypersensitivity against ionized radiation with the tendency to develop cancer related to progressive cerebellar ataxia, pathognomonic oculocutaneous telangiectasias, varying degrees of humoral and cellular immunodeficiency, and infertility. This case report presents a 3-year-old male patient with A-T who developed hemophagocytic syndrome. To the best of our knowledge, no such case has been previously reported.