Birth Size in Neonates with Congenital Adrenal Hyperplasia due to 21-hydroxylase Deficiency.

Objective: Classic congenital adrenal hyperplasia (CAH) secondary to 21-hydroxylase deficiency is characterized by increased prenatal adrenal androgen secretion. There are a small number of reports in the literature showing higher birth weight and length in CAH newborns.

Methods: We analyzed birth weight and length data of 116 German newborns (48 boys, 68 girls) with classic CAH who were born during the period from 1990 to 2017.

Adrenal crisis in a 14-year-old boy 12 years after hematopoietic stem cell transplantation.

Unlabelled: We report on a boy of Albanian descent with the history of juvenile myelomonocytic leukemia (JMML). JMML was diagnosed at the age of 17 months and treated by hematopoietic stem cell transplantation (HSCT). At the age of 14.

Short-term adverse effects of testosterone used for priming in prepubertal boys before growth hormone stimulation test.

Background: Despite the fact that priming with sex steroids in prepubertal children before growth hormone (GH) provocative tests is recommended, there is an ongoing controversial discussion about the appropriate age of the children, the drug used for priming, the dose and the period between priming and the GH test. Interestingly, there is no discussion on the safety of this procedure. To date, only little data have been available on the possible side effects of priming with testosterone.

Mutant Hoxd13 induces extra digits in a mouse model of synpolydactyly directly and by decreasing retinoic acid synthesis.

Individuals with the birth defect synpolydactyly (SPD) have 1 or more digit duplicated and 2 or more digits fused together. One form of SPD is caused by polyalanine expansions in homeobox d13 (Hoxd13). Here we have used the naturally occurring mouse mutant that has the same mutation, the SPD homolog (Spdh) allele, and a similar phenotype, to investigate the molecular pathogenesis of SPD.

Large-scale mapping of mutations affecting zebrafish development.

Background: Large-scale mutagenesis screens in the zebrafish employing the mutagen ENU have isolated several hundred mutant loci that represent putative developmental control genes. In order to realize the potential of such screens, systematic genetic mapping of the mutations is necessary. Here we report on a large-scale effort to map the mutations generated in mutagenesis screening at the Max Planck Institute for Developmental Biology by genome scanning with microsatellite markers.

The other trinucleotide repeat: polyalanine expansion disorders.

Expansions of trinucleotide repeats encoding polyalanine tracts have been recognized as the cause of several diseases, predominantly congenital malformation syndromes. To date, nine genes with alanine tract expansions have been described. With the exception of PABPN1, which codes for a poly(A)-binding protein, all these genes encode transcription factors that play important roles during development.

A molecular pathogenesis for transcription factor associated poly-alanine tract expansions.

Poly-alanine (Ala) tract expansions in transcription factors have been shown to be associated with human birth defects such as malformations of the brain, the digits, and other structures. Expansions of a poly-Ala tract from 15 to 22 (+7)-29 (+14) Ala in Hoxd13, for example, result in the limb malformation synpolydactyly in humans and in mice [synpolydactyly homolog (spdh)]. Here, we show that an increase of the Ala repeat above a certain length (22 Ala) is associated with a shift in the localization of Hoxd13 from nuclear to cytoplasmic, where it forms large amorphous aggregates.

The synpolydactyly homolog (spdh) mutation in the mouse -- a defect in patterning and growth of limb cartilage elements.

We have investigated the recessive mouse mutant synpolydactyly homolog (spdh) as a model for human synpolydactyly (SPD). As in human SPD, the spdh phenotype consists of central polydactyly, syndactyly and brachydactyly and is caused by the expansion of a polyalanine encoding repeat in the 5' region of the Hoxd13 gene. We performed a detailed phenotypic and functional analysis of spdh/spdh embryos using skeletal preparations, histology, in situ hybridization, BrdU labeling of proliferating cells, and in vitro expression studies.