Holoprosencephaly due to mutations in ZIC2: alanine tract expansion mutations may be caused by parental somatic recombination.

We report on the prevalence of mutations in the zinc finger transcription factor gene, ZIC2, in a group of 509 unrelated individuals with isolated holoprosencephaly (HPE) and normal chromosomes. Overall, we encountered 16 HPE patients (from 15 unrelated families) with ZIC2 mutations. Thus, ZIC2 mutation was the apparent cause of HPE in 3-4% of cases.

Genotypic and phenotypic spectrum in tricho-rhino-phalangeal syndrome types I and III.

Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities. Three subtypes have been described: TRPS I, caused by mutations in the TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. To investigate whether TRPS III is caused by TRPS1 mutations and to establish a genotype-phenotype correlation in TRPS, we performed extensive mutation analysis and evaluated the height and degree of brachydactyly in patients with TRPS I or TRPS III.

Formation of supernumerary euchromatic short arm isochromosomes: parent and cell stage of origin in new cases and review of the literature.

In order to get insight in the formation of isochromosomes we analysed different supernumerary euchromatic short arm isochromosomes for the parent and cell stage of origin. After cytogenetic detection and confirmation by fluorescence-in-situ hybridization we performed short tandem repeat typing in a child with i(9p), three with i(12p) and three with i(18p). The extra chromosomes were monocentric in each case, the i(9p) and i(12p) constitutions were found in mosaic with normal cell lines.

Multiplex-FISH for pre- and postnatal diagnostic applications.

For >3 decades, Giemsa banding of metaphase chromosomes has been the standard karyotypic analysis for pre- and postnatal diagnostic applications. However, marker chromosomes or structural abnormalities are often encountered that cannot be deciphered by G-banding alone. Here we describe the use of multiplex-FISH (M-FISH), which allows the visualization of the 22 human autosomes and the 2 sex chromosomes, in 24 different colors.

Two brothers with multiple congenital anomalies and mental retardation due to disomy (X)(q12-->q13.3) inherited from the mother.

We present the phenotypic, cytogenetic and molecular findings in two dysmorphic and mentally retarded brothers with disomy Xq12-->q13.3. The mother and the grandmother carry the same rearrangement of the X chromosome, which was interpreted as an inverted insertion of the segment (X)(q12-->q13.

The fragile-X phenotype. Computer assisted analysis of the dysmorphological features and discrimination from the Sotos phenotype.

Fragile-X and Sotos phenotypes may be difficult to distinguish. This is illustrated with a case report. Computer assisted phenotype analyses (MDDB), using the complete trait list of this patient, suggested the fragile-X diagnosis, which later was confirmed by molecular techniques.

Partial trisomy 8q. Two case reports with maternal translocation and inverted insertion: phenotype analyses and reflections on the risk.

Partial trisomy 8qter-->q23 or q24.1 has been reported in 15 literature cases. We add two further case reports here.