Dominant mutation causes neurological disorder with ichthyotic keratoderma, spasticity, hypomyelination and dysmorphic features.

Background: Ichthyosis and neurological involvement occur in relatively few known Mendelian disorders caused by mutations in genes relevant both for epidermis and neural function.

Objectives: To identify the cause of a similar phenotype of ichthyotic keratoderma, spasticity, mild hypomyelination (on MRI) and dysmorphic features (IKSHD) observed in two unrelated paediatric probands without family history of disease.

Methods: Whole exome sequencing was performed in both patients.

Audio profiles in mitochondrial deafness m.1555A>G and m.3243A>G show distinct differences.

Background: Hearing loss is one of the most common symptoms of mitochondrial disorders. However, audiological phenotypes associated with different molecular defects in mtDNA are not yet well characterized.

Material And Methods: A large cohort of 1499 nonconsanguineous patients aged 5-40 years with hearing loss of unknown etiology was screened for mutations in mtDNA.

Application of array comparative genomic hybridization in 256 patients with developmental delay or intellectual disability.

We used whole-genome exon-targeted oligonucleotide array comparative genomic hybridization (array CGH) in a cohort of 256 patients with developmental delay (DD)/intellectual disability (ID) with or without dysmorphic features, additional neurodevelopmental abnormalities, and/or congenital malformations. In 69 patients, we identified 84 non-polymorphic copy-number variants, among which 41 are known to be clinically relevant, including two recently described deletions, 4q21.21q21.

Postlingual hearing loss as a mitochondrial 3243A>G mutation phenotype.

Background: The prevalence of isolated hearing loss (HL) associated with the m.3243A>G mutation is unknown. The aim of this study was to assess the frequency and heteroplasmy level of the m.

MTHFR 677T is a strong determinant of the degree of hearing loss among Polish males with postlingual sensorineural hearing impairment.

Hearing impairment (HI) is the most common sensory handicap. Congenital HI often has a genetic basis, whereas the etiology of nonsyndromic postlingual HI (npHI) usually remains unidentified. Our purpose was to test whether the MTHFR C677T (rs1801133) polymorphism affecting folate metabolism is associated with the occurrence or severity of npHI.

Wolf-Hirschhorn syndrome due to pure and translocation forms of monosomy 4p16.1 → pter.

The aim of this study was to obtain a quantitative definition of Wolf-Hirschhorn syndrome (WHS) through systematic phenotypic analyses in a group of six children with 4p15.32 → pter, 4p15.33 → pter, or 4p16.

Subtelomeric rearrangements in Polish subjects with intellectual disability and dysmorphic features.

Fluorescent in situ hybridization (FISH) was performed in 76 patients referred to our department because of intellectual disability and dysmorphic features that can be related to subtelomeric microaberrations. In all the patients, conventional cytogenetic methods revealed normal karyotype. Four (5.

Mild Smith-Lemli-Opitz syndrome: further delineation of 5 Polish cases and review of the literature.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder caused by reduced activity of 7-dehydrocholesterol reductase, resulting in an increased concentrations of 7-dehydrocholesterol and 8-dehydrocholesterol in body fluids and tissues. Phenotypically it is characterized by wide range of abnormalities, from mild to lethal forms what causes difficulties in its clinical diagnostics. To further delineate the physical spectrum of the mild form of Smith-Lemli-Opitz syndrome, especially with regard to genotype-phenotype correlation, we describe 5 Polish patients with mild phenotype (one with novel mutation in DHCR7 gene and four published before) and analyze 18 other cases from the literature.

Complex balanced translocation t(1;5;7)(p32.1;q14.3;p21.3) and two microdeletions del(1)(p31.1p31.1) and del(7)(p14.1p14.1) in a patient with features of Greig cephalopolysyndactyly and mental retardation.

Complex chromosome rearrangements (CCRs) are rare structural abnormalities that involve at least two chromosomes and more than two breakpoints and are often associated with developmental delay, mental retardation, and congenital anomalies. We report on a de novo, apparently balanced translocation t(1;5;7)(p32.1;q14.

M34T and V37I mutations in GJB2 associated hearing impairment: evidence for pathogenicity and reduced penetrance.

Despite research the role of the M34T and V37I variants of GJB2 in causing hearing impairment (HI) remains controversial. Our purpose was to test a hypothesis that M34T and V37I are pathogenic but have distinct features resulting in a reduced penetrance. We screened for known GJB2/GJB6 mutations 233 Polish consecutive unrelated subjects with non-syndromic, sensorineural HI who were previously found to carry 35delG mutation on one chromosome.

Molecular background of polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome in a Polish population: novel AIRE mutations and an estimate of disease prevalence.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autosomal-recessive autoimmune disease caused by autoimmune regulator gene mutations. The aim of this study was to examine the mutation profile of Polish APECED patients, determine the carrier rate of the most frequent mutation(s) and estimate disease prevalence. While studying 14 unrelated patients, we identified three novel mutations (c.

Congenital anomalies and developmental delay in a boy with double chromosome 6 derived supernumerary marker.

The frequency of small supernumerary marker chromosomes has been estimated to approximately 0.45 per 1000 newborns. They are usually seen as single marker chromosomes in a mosaic state.

Fibular aplasia with ectrodactyly--broadening the clinical spectrum.

Fibular aplasia-ectrodactyly is a rare disorder of the central axis, characterized by shortening of the affected limbs and formation of split hand and/or foot. Here we report on a severely affected case of fibular aplasia with ectrodactyly, in which the upper limb malformations are more pronounced than usually described in sporadic cases.

Thrombocytopenia-absent radius (tar) syndrome: a case with agenesis of corpus callosum, hypoplasia of cerebellar vermis and horseshoe kidney.

The thrombocytopenia-absent radius (TAR) syndrome (MIM 274000) is a congenital malformation syndrome characterised by bilateral absence of the radii with present thumbs, hypomegakaryocytic thrombocytopenia and a number of additional features including skeletal and cardiac anomalies. Mental retardation, reported in about 7% of patients, is usually secondary to intracranial hemorrhage. In 1994 there was a single report of a girl with TAR syndrome and hypoplasia of the cerebellar vermis and corpus callosum and in 2003 another case of TAR syndrome with cerebellar dysgenesis has been reported.

Aldolase B mutations and prevalence of hereditary fructose intolerance in a Polish population.

We studied 28 Polish hereditary fructose intolerant (HFI) patients (26 unrelated) by direct sequencing of the ALDOB coding region/splice sites. Eight different mutations were found including two novel ones (each found in two unrelated individuals): c.250delC (frameshift) and c.

Fatal primary pulmonary hypertension in a 30-yr-old female with APECED syndrome.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by mutations in the autoimmune regulator (AIRE) gene, which has a central function in maintaining immunological tolerance. A number of conditions with proven or likely autoimmune pathogenesis occur in APECED: hypoparathyroidism, adrenocortical insufficency, candidiasis, hypogonadism, type 1 diabetes, hypothyroidism, hypophysitis, hepatitis, malabsorption, nail dystrophy, enamel hypoplasia and keratopathy. It is not clear which factors are responsible for variation in clinical picture of APECED, but human leukocyte antigen (HLA) genotype may be important.

Two familial cases with a lethal gracile bone dysplasia and intrauterine growth retardation.

A number of more or less distinct entities with low birth weight and abnormal radiographic appearances have been identified. We studied two sisters who were unusual because of severe intrauterine growth restriction, absence of growth after birth, decrease of pre- and postnatal spontaneous mobility, and early fatal outcome. The chondro-osseous morphology documented a distinctive osteochondrodysplasia.

Proteus syndrome: a case with clonal chromosome aberration.

Proteus syndrome is a disorder characterized by overgrowth of multiple tissues, connective tissue nevi, epidermal nevi and hyperostoses with asymmetric involvement. The clinical expression of the disorder is extremely variable. Molecular pathogenesis of the syndrome is unknown but it is hypothesized that it resulted from a somatic alteration of a gene leading to mosaic effects that would be lethal if the mutation was carried in nonmosaic fashion, and this may explain the variability among patients.

Increase in the incidence of type 1 diabetes mellitus in children in three cities in Poland, 1987-1999.

The aim of this study was to evaluate the trends in the incidence of type 1 diabetes mellitus (DM) in children aged 0-14 years between 1987 and 1999 in three cities in Poland. The study area comprised the provinces of Cracow and Wroclaw and the city of Warsaw. The data were collected prospectively on the basis of the register within the framework of the EURODIAB study up till 1997 and then within the project of the Ministry of Health.

[Polish multicenter study on diabetes type I incidence in he age group 0-14 between 1998 and 1999].

The increase in diabetes type 1 incidence observed in various centers in Poland and the need for a centralized study covering large population have resulted in the construction of a standardized registry of type 1 diabetes in 1998 within the Polish Multicenter Study in Diabetes Epidemiology. The aim of the study was to present the incidence rates of type 1 diabetes in the age group 0-14 in 7 distinct regions of Poland (Krakow, Wroclaw, Warsaw, Bialystok, Poznan, Rzeszow and Olsztyn centers) with over 30% of the Polish population at risk in 1998 and 1999. The data for the standardized registry were obtained prospectively from paediatric hospital wards and diabetes outpatient units.

Wiedemann-Rautenstrauch (neonatal progeroid) syndrome: new case with normal telomere length in skin fibroblasts.

Wiedemann-Rautenstrauch (neonatal progeroid) syndrome is an autosomal recessive condition with characteristic appearance of premature aging present at birth (aged face, natal teeth, and wrinkled skin). Other features of the syndrome are generalized lipoatrophy with specific fat accumulation in the lateral suprabuttock region, hypotrichosis, macrocephaly (pseudohydrocephalus), and mental retardation. We report on a new case that demonstrates all typical features of the syndrome.