Identification of copy number variants associated with BPES-like phenotypes.

Blepharophimosis-Ptosis-Epicanthus inversus syndrome (BPES) is a well-characterized rare syndrome that includes an eyelid malformation associated with (type I) or without premature ovarian failure (type II). Patients with typical BPES have four major characteristics: blepharophimosis, ptosis, epicanthus inversus and telecanthus. Mutations in the FOXL2 gene, encoding a forkhead transcription factor, are responsible for the majority of both types of BPES.

Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure.

Background: DNA Ligase IV deficiency syndrome is a rare autosomal recessive disorder caused by hypomorphic mutations in the DNA ligase IV gene (LIG4). The clinical phenotype shows overlap with a number of other rare syndromes, including Seckel syndrome, Nijmegen breakage syndrome, and Fanconi anemia. Thus the clinical diagnosis is often delayed and established by exclusion.

Childhood overgrowth in patients with common NF1 microdeletions.

While growth retardation and short stature are well-known features of patients with classical neurofibromatosis type 1 (NF1), we found advanced height growth and accelerated carpal bone age in patients with an NF1 microdeletion. Our analysis is based on growth data of 21 patients with common 1.4/1.

Idiopathic hyperphosphatasia and TNFRSF11B mutations: relationships between phenotype and genotype.

Unlabelled: Homozygous mutations in TNFRSF11B, the gene encoding osteoprotegerin, were found in affected members from six of nine families with idiopathic hyperphosphatasia. The severity of the phenotype was related to the predicted effects of the mutations on osteoprotegerin function.

Introduction: Idiopathic hyperphosphatasia (IH) is a rare high bone turnover congenital bone disease in which affected children are normal at birth but develop progressive long bone deformities, fractures, vertebral collapse, skull enlargement, and deafness.

Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients.

Classical citrullinemia (CTLN1), a rare autosomal recessive disorder, is caused by mutations of the argininosuccinate synthetase (ASS) gene, localized on chromosome 9q34.1. ASS functions as a rate-limiting enzyme in the urea cycle.

DHPLC mutation analysis of phenylketonuria.

Denaturing high-performance liquid chromatography (DHPLC) is a sensitive and fast method for the detection of mutations which has been successfully used for mutation screening in several disease-related genes. Phenylketonuria (PKU, OMIM* 261600; McKusick 1986) is one of the most common autosomal recessive disorders in Europe. Mutations in the PAH gene mainly involve point mutations.

A mutation in the gene TNFRSF11B encoding osteoprotegerin causes an idiopathic hyperphosphatasia phenotype.

Idiopathic hyperphosphatasia is an autosomal recessive bone disease characterized by deformities of long bones, kyphosis and acetabular protrusion, increasing in severity as affected children pass through adolescence. Biochemical and histological evidence indicate that there is extremely rapid bone turnover, with indices of both bone resorption and formation greatly increased. A genome-wide search, in a family with three children affected by idiopathic hyperphosphatasia, suggested linkage to a locus on the long arm of chromosome 8 (8q24).