Spectrum of FOXL2 gene mutations in blepharophimosis-ptosis-epicanthus inversus (BPES) families demonstrates a genotype-phenotype correlation

Mutations in FOXL2, a forkhead transcription factor gene, have recently been shown to cause blepharo-phimosis-ptosis-epicanthus inversus syndrome (BPES) types I and II, a rare genetic disorder. In BPES type I a complex eyelid malformation is associated with premature ovarian failure (POF), whereas in BPES type II the eyelid defect occurs as an isolated entity. In this study, we describe the identification of novel mutations in the FOXL2 gene in BPES types I and II families, in sporadic BPES patients, and in BPES families where the type could not be established. In 67% of the patients studied, we identified a mutation in the FOXL2 gene. In total, 21 mutations (17 of which are novel) and one microdeletion were identified. Thirteen of these FOXL2 mutations are unique. In this study, we demonstrate that there is a genotype-phenotype correlation for either types of BPES by the finding that mutations predicted to result in a truncated protein either lacking or containing the forkhead domain lead to BPES type I. In contrast, duplications within or downstream of the forkhead domain, and a frameshift downstream of them, all predicted to result in an extended protein, cause BPES type II. In addition, in 30 unrelated patients with isolated POF no causal mutations were identified in FOXL2. Our study provides further evidence that FOXL2 haploinsufficiency may cause BPES types I and III by the effect of a null allele and a hypomorphic allele, respectively. Furthermore, we propose that in a fraction of the BPES patients the genetic defect does not reside within the coding region of the FOXL2 gene and may be caused by a position effect

CHARGE association in a neonate exposed in utero to carbon monoxide.

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Association between Down syndrome and portohepatic shunt

SCOPUS: le.jinfo:eu-repo/semantics/publishe

Maternal diabetes and fetal malformations: A case associating cardiovascular, facial and skeletal malformations

Maternal diabetes is known to be a condition associated with a high frequency of fetal malformations. However, pathogenic factors for these malformations and their possible classification into different entities are not yet well established. We present the case of an infant born to a diabetic mother and affected by several malformations. This report consolidates different hypotheses put forward in recent years.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Development of a new sensitive ELISA for the determination of uteroglobin-related protein 1, a new potential biomarker

Uteroglobin-related protein 1 (UGRP-1) is a protein specifically secreted in airways, where it could play an anti-inflammatory role. We developed a sandwich enzyme-linked immunosorbent assay (ELISA) allowing the detection of UGRP-1 in serum, urine, and amniotic and pulmonary fluids. Concentrations of UGRP-1 determined by ELISA and latex immunoassay were correlated in sputum and bronchoalveolar lavage fluid (BALF). The pattern of UGRP-1 concentration resembled that of Clara cell protein, both proteins occurring in high concentrations in amniotic fluid, sputum and BALF and in much lower concentrations in serum and urine. These findings suggest that UGRP-1 might serve as a biomarker of respiratory epithelium integrity

New syndrome or severe expression of Gordon syndrome? A case report.

A boy with multiple congenital anomalies including median cleft palate, bilateral hearing loss, clino- and camptodactyly, bilateral single palmar flexion creases, severe hypotonia with kyphoscoliosis and respiratory insufficiency, failure to thrive, bilateral cryptorchidism and facial dysmorphism (epicanthus, a flat nasal bridge, a small mouth, a small nose with anteverted nostrils, low-set ears, a prominent forehead, microretrognathia) is presented. His mother has a median cleft palate, bilateral hearing loss, single palmar flexion creases, and short stature. An autosomal or X-linked dominant syndrome with more severe expression in the proband than in his mother is suggested.Case ReportsJournal Articleinfo:eu-repo/semantics/publishe

Oculocerebral hypopigmentation syndrome (Cross syndrome) in a Gipsy child

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Further evidence for autosomal dominant inheritance and ectodermal abnormalities in Kabuki syndrome

Most cases with Kabuki syndrome (KS) were reported sporadically. Recently, a few familial cases of KS were reported. This report provides further evidence that the KS is inherited as a dominant trait with variable expressivity. The proposita is an 18-month-old girl with facial findings characteristic of Kabuki syndrome, prominent fingertippads, a midsagittal cleft of vertebral body D4, hypotonia, and psychomotor retardation. Her mother had a similar facial appearance, prominent, cup-shaped ears, an abnormal dentition, early breast development, and low-normal intelligence. Because mother and daughter both had evident Kabuki syndrome, we conclude that KS in this family is inherited as a dominant trait. Further family history supports this finding. Microscopic examination of the hair of the proposita shows abnormalities consisting of trichorrhexis nodosa, twisting of the hair-shafts, and irregularity of the diameter of the hair, as was described recently in a patient with KS. This could be another occasional finding in this syndrome, but further studies are required. The presence of abnormal hair, nails, and the commonly described tooth abnormalities in KS further suggest ectodermal involvement in this syndrome. (C) 2000 Wiley-Liss, Inc.SCOPUS: ar.jinfo:eu-repo/semantics/publishe