The smallest de novo deletion of 20q11.21-q11.23 in a girl with feeding problems, retinal dysplasia, and skeletal abnormalities.

We report on a de novo interstitial deletion of 20q11.21-q11.23 in a 2-year-old girl with a set of dysmorphic features, cleft palate, heart defect, severe feeding problems, failure to thrive, developmental delay, preaxial polydactyly (right thumb), and retinal dysplasia. Interstitial microdeletions of the long arm of chromosome 20 are rare. Exclusively rare are proximal microdeletions involving 20q11-q12 region. Our patient is the fourth described so far and has the smallest deleted region 20q11.21-q11.23 of 5.7 Mb. The defined clinical phenotype of our patient is very similar to previously published cases and confirms the existence of retinal dysplasia and skeletal abnormalities as a part of phenotypic spectrum for deletion 20q11-q12. Description of four similar patients, including two almost identical, suggests a new distinct, phenotypicaly recognizable microdeletion syndrome associated with the loss of 20q11-q12 region.

New case of Primrose syndrome with mild intellectual disability.

We report on a 27-year-old man, who represents the sixth and the youngest published case of Primrose syndrome. Primrose syndrome (PS) (OMIM#295090) is an extremely rare entity of unknown etiology characterized by the progressive wasting of distal muscles of the legs, the small muscles of the hands resulting in contractures, the presence of intellectual disability, hearing problems, cataracts, brain calcification, and the ossification of ear cartilage. All the main manifestations were present in our patient. Despite the phenotypic similarity to five other cases, our patient had mild intellectual disability. Additionally we found hypergonadotropic hypogonadism and a low bone density due to progressive osteoporosis. We discuss our observations in relation to previously published cases, and we stress the need for the detail and phenotypic descriptions of further cases as PS remains rare, and the genetic basis is still undiscovered.

[Gap junction intercellular communication in carcinogenesis of endometrial cancer]. / Komunikacja miedzykomórkowa z udzialem polaczen typu gap w karcinogenezie blony sluzowej trzonu macicy.

One of the mechanisms for direct cell to cell signaling is mediated by gap junctions. These junctions are formed by connexins, transmembrane proteins. Gap junction intercellular communication (GJIC) plays a critical role in tissue development, differentiation of cells, and regulation of tissue homeostasis. Cancer cells are characterized by growth and/or differentiation disorders. Endometrial cancer is the most common gynecological malignancy in developed countries. In this study we discuss the putative role of GJIC and adhesion molecules in the development of endometrial cancer The relationships of GJIC to the process of apoptosis and function of some adhesion proteins have also been underlined.

The natural history of Möbius syndrome in a 32-year-old man.

Möbius syndrome (OMIM#157900) is an extremely rare congenital entity involving bilateral or unilateral palsy of the facial nerve, usually with dysfunction of other cranial nerves (second, third, fifth, sixth, ninth, tenth and twelfth). It was estimated that Möbius syndrome occurs in 1 of 50 000 live births. The aetiology and the pathogenesis of the syndrome remain unknown. The majority of published cases were sporadic. We report on the natural history of a 32-year-old man with de novo Möbius syndrome. The diagnosis was established at the age of 9 months due to partial bilateral facial and abducent nerve palsy. Additionally, the patient demonstrated failure to thrive during infancy and childhood, many dysmorphic features, lower limb anomalies, and hypogonadism in adulthood, but his intelligence was in the normal range. The low quality of life of the patient with Möbius syndrome is emphasized.

IGF-IR in patients with advanced colorectal cancer in correlation with certain clinico-morphological factors: Initial report.

The insulin-like growth factor (IGF) system comprises two types of peptides (IGF-I and IGF-II), two types of receptors (IGF-IR and IGF-IIR) and six IGF-binding proteins (BP). This system is mainly responsible for the growth and division of cells in the body, regulation of the cell cycle and prevention of apoptosis. The expression of IGF-IR was assessed in the cells of resected primary colorectal tumours in 88 patients (age, 36-87 years; mean 64.78; males, 48 and females, 40) treated surgically at the Second Department of General and Gastroenterological Surgery, Medical University of Bialystok, Poland, in relation to various clinico-morphological factors. The post-operative material was analysed to find the histological type, location of lesions, lymph node involvement staging, distant metastases (pTNM classification), staging in Dukes' classification and the histopathological differentiation grade. The expression of IGF-IR in colorectal cancer cells was assessed using an immunohistochemical method. The findings were subjected to statistical analysis (Chi-square test, multivariation test and Mann-Whitney U test). A positive IGF-IR expression (in at least 10% of cancer cells) was observed in 44 patients. The mean immunoreactive cell count for IGF-IR in all of the tumours studied was 30.79%. The current study showed no correlation of IGF-IR expression in colorectal cancer cells with characteristics such as age and gender of patients, tumour location, type, histological differentiation or histopathological advancement. Immunohistological determination of IGF-IR expression in advanced colorectal cancer cells revealed controversial scores. Evaluation should be confirmed by using other methods and enhanced to include adenomas and early colorectal cancers.

Risk evaluation of carriers with chromosome reciprocal translocation t(7;13)(q34;q13) and concomitant meiotic segregation analyzed by FISH on ejaculated spermatozoa.

We performed the segregation analysis of a relatively large pedigree of t(7;13)(q34;q13) carriers together with the sperm karyotype analysis of the one carrier using a tri-color fluorescence in situ hybridization (FISH) method. The risk assessments for unfavorable pregnancy outcomes in a series of 36 pregnancies in eight reciprocal chromosome translocation (RCT) couples of carriers were estimated directly from a pedigree after ascertainment correction. The individual probability rate for unbalanced child was predicted according to Stengel-Rutkowski and co-workers. The unbalanced karyotypes in the form of monosomy 7q34-->qter and trisomy 13q13-->qter were detected among stillborn/early death newborns with holoprosencephaly (HPE), cyclopia and other malformations. Based on clinical description of unkaryotyped stillbirth progeny, it can be assumed that the phenotype distinctions were connected with the unbalanced karyotype from 2:2 segregation (monosomy 7q with trisomy 13q) and 3:1 segregation as interchange trisomy 13 (Patau syndrome). Probability rates for miscarriages, stillbirth/early death were 12.9 +/- 6% (4/31) and 29 +/- 8.2% (9/31), respectively. The results of the meiotic segregation pattern indicated the rate of unbalanced spermatozoa for about 60%, with the unusual high rate (29.4%) of 3:1 segregant (i.e., 13.4% of the tertiary segregation and 16% of the interchange segregation). Adjacent-1 segregation followed with 23.5% and adjacent-2 followed with 7.2% of analyzed spermatozoa. The high rate of unbalanced gametes in comparison to the number of stillborn/early death and miscarriages detected in pedigree suggests a strong selection against unbalanced chromosomal constitutions during fetal development. It corresponds to a very small probability rate (about 0.3%) of viable unbalanced progeny from 3:1 meiotic segregation predicted for maternal carriers. This knowledge can be used in genetic counseling of families with similar RCT ascertained in a different way.

[Microphthalmos and hypertelorism as diagnostic index in ultrasound diagnosis of Fraser syndrome]. / Maloocze i szerokie rozstawienie galek ocznych w obrazie usg jako wskaznik diagnostyczny obecnosci zespolu Frasera u plodu.

Fraser syndrome is a rare genetic syndrome with abnormalities of the head, lungs, kidneys, and limbs. A prenatal diagnosis of FS can be done in families with risk, using foetal ultrasonography. However, a wide qualitative and quantitative variability of possible abnormalities makes the diagnosis in utero notably questionable. We present the results of foetal ultrasonography in a tertigravida, had delivered two children with FS. Signs of foetal hypertelorism and microphthalmia, both traits typical for FS, were detected based on outer and inner orbital diameters and ocular diameters in 28 and 32 weeks of pregnancy. The clinical and pathological examinations after birth confirmed the diagnosis of FS. Our observation suggests that eye anomalies may prompt the diagnosis of FS even if characteristic lung and kidney abnormalities are absent. Therefore, we propose to regularly assess eye dimensions and distance, when performing any foetal ultrasonography in families with of FS.

A novel Gly to Arg substitution at position 388 of the alpha1 chain of type I collagen in lethal form of osteogenesis imperfecta.

Cultured skin fibroblasts from a proband with a lethal form of osteogenesis imperfecta produce two forms of type I collagen chains, with normal and delayed electrophoretic migration; collagen of the proband's mother was normal. Peptide mapping experiments localized the structural defect in the proband to alpha1(I) CB8 peptide in which residues 123 to 402 are spaned. Direct sequencing of amplified cDNA covering this region revealed a G to A single base change in one allele of the alpha1(I) chain, that converted glycine 388 to arginine. Restriction enzyme digestion of the RT-PCR product was consistent with a heterozygous COL1A1 mutation. The novel mutation conforms to the linear gradient of clinical severity for the alpha1(I) chain and results in reduced thermal stability by 3 degrees C and intracellular retention of abnormal molecules.