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Biomedical subjects

J Amiel

Publications and source records attributed to J Amiel.

At least 73 records · Page 4Linked to original sources
PubMed1999

Unreported RSK2 missense mutation in two male sibs with an unusually mild form of Coffin-Lowry syndrome.

An unreported missense mutation of the ribosomal S6 kinase 2 (RSK2) gene has been identified in two male sibs with a mild form of Coffin-Lowry syndrome (CLS) inherited from their healthy mother. They exhibit transient severe hypotonia, macrocephaly, delay in closure of the fontanelles, normal gait, and mild mental retardation, associated in the first sib with transient autistic behaviour. Some dysmorphic features of CLS (in particular forearm fullness and tapering fingers) and many atypical findings (some of which were reminiscent of FG syndrome) were observed as well. The moderate phenotypic expression of this mutation extends the CLS phenotype to include less severe mental retardation and minor, hitherto unreported signs. The missense mutation identified may be less deleterious than those previously described. As this mutation occurs in a protein domain with no predicted function, it could be responsible for a conformational change affecting the protein catalytic function, since a non-polar amino acid is replaced by a charged residue.

Abnormalities, Multiple↗
PubMed1999

Epiphyseal, vertebral, and ear (EVE) dysplasia: a new syndrome?

We report on the association of epiphyseal, vertebral, and ear dysplasia in two sisters with normal stature and psychomotor development born to distantly related, healthy parents. This distinctive association has not been reported previously and is likely to represent a new condition with an autosomal recessive mode of inheritance. For this syndrome, we propose the acronym EVE standing for epiphyseal, vertebral, and ear dysplasia.

Child↗
PubMed1998

Expression of the RET proto-oncogene in human embryos.

The patterns of RET proto-oncogene expression in mouse, rat, and chicken and the anomalies observed in targeted RET mutants suggest that RET plays a major role in development of mouse enteric nervous system and in kidney organogenesis. Here, we report on in situ hybridization studies describing the pattern of RET proto-oncogene expression during early development of human embryos between 23 and 42 days. We show that the RET gene is expressed in the developing kidney (nephric duct, mesonephric tubules, and ureteric bud), the presumptive enteric neuroblasts of the developing enteric nervous system, cranial ganglia (VII+VIII, IX, and X) and in the presumptive motor neurons of the spinal cord. Yet, despite the high level of RET gene expression in the kidney and in the motor neurons of the developing central nervous system in human embryos, only rare cases with renal agenesis have been reported in Hirschsprung disease patients, and no clinical evidence of spinal cord involvement has been shown in patients carrying RET germline mutations (i.e., multiple endocrine neoplasia syndromes and Hirschsprung disease).

Central Nervous System↗
PubMed1998

Ebstein anomaly associated with rearrangements of chromosomal region 11q.

Ebstein anomaly (EA) is a relatively uncommon congenital heart defect and it is very rarely associated with a chromosomal anomaly. We report two distinct rearrangements of the chromosomal region 11q arm in two unrelated patients with Ebstein anomaly, renal malformation, minor anomalies, and the Pierre Robin sequence. The first patient had an interstitial deletion of chromosome 11 [46,XY,del(11)(11q21q23), and the other had a tertiary trisomy of chromosome 11qter (47,XX,+der(22)t(11;22)(q23;q11.2) Its association with either a chromosome 11q deletion or a duplication in some individuals suggests that a rearrangement of the 11q region is likely to cause a shift of the individuals' underlying liability to develop EA above a certain threshold.

Chromosome Aberrations↗
PubMed1998

CHARGE syndrome: report of 47 cases and review.

The acronym CHARGE refers to a syndrome of unknown cause. Here we report on 47 CHARGE patients evaluated for the frequency of major anomalies, namely coloboma (79%), heart malformation (85%), choanal atresia (57%), growth and/or mental retardation (100%), genital anomalies (34%), ear anomalies (91%), and/or deafness (62%). In addition, we comment on anomalies observed very frequently in neonates and infants with the CHARGE syndrome, including, minor facial anomalies, neonatal brain stem dysfunction with cranial nerve palsy, and, mostly, internal ear anomalies such as semicircular canal hypoplasia that were found in each patient that could be tested. We propose several criteria for poor survival including male gender, central nervous system and/or oesophageal malformations, and bilateral choanal atresia. No predictive factor regarding developmental prognosis could be identified in our series. A significantly higher mean paternal age at conception together with concordance in monozygotic twins and the existence of rare familial cases support the role of genetic factors such as de novo mutation of a dominant gene or subtle sub-microscopic chromosome rearrangement. Finally, the combination of malformations in CHARGE syndrome strongly supports the view that this multiple congenital anomalies/mental retardation syndrome is a polytopic developmental field defect involving the neural tube and the neural crests cells.

Abnormalities, Multiple↗
PubMed1998

SOX10 mutations in patients with Waardenburg-Hirschsprung disease.

Waardenburg syndrome (WS; deafness with pigmentary abnormalities) and Hirschsprung's disease (HSCR; aganglionic megacolon) are congenital disorders caused by defective function of the embryonic neural crest. WS and HSCR are associated in patients with Waardenburg-Shah syndrome (WS4), whose symptoms are reminiscent of the white coat-spotting and aganglionic megacolon displayed by the mouse mutants Dom (Dominant megacolon), piebald-lethal (sl) and lethal spotting (ls). The sl and ls phenotypes are caused by mutations in the genes encoding the Endothelin-B receptor (Ednrb) and Endothelin 3 (Edn3), respectively. The identification of Sox10 as the gene mutated in Dom mice (B.H. et al., manuscript submitted) prompted us to analyse the role of its human homologue SOX10 in neural crest defects. Here we show that patients from four families with WS4 have mutations in SOX10, whereas no mutation could be detected in patients with HSCR alone. These mutations are likely to result in haploinsufficiency of the SOX10 product. Our findings further define the locus heterogeneity of Waardenburg-Hirschsprung syndromes, and point to an essential role of SOX10 in the development of two neural crest-derived human cell lineages.

Amino Acid Sequence↗
PubMed1998

Mutation of the RET ligand, neurturin, supports multigenic inheritance in Hirschsprung disease.

Hirschsprung disease (HSCR) is a frequent neurocristopathy characterized by the absence of submucosal and myenteric plexuses in a variable length of the gastrointestinal tract. Pedigrees and segregation analyses suggested the involvement of one or several dominant genes with low penetrance in HSCR. Considering that RET and glial cell line-derived neurotrophic factor (GDNF) mutations have been reported in the disease, we regarded the other RET ligand, neurturin (NTN), as an attractive candidate gene, especially as it shares large homologies with GDNF. Here, we report on the finding of a heterozygous missense NTN mutation in a large non-consanguineous family including four children affected with a severe aganglionosis phenotype extending up to the small intestine. Interestingly, it appears that the NTN mutation reported here is not sufficient to cause HSCR, and this multiplex family also segregates a RET mutation. This cascade of independent and additive genetic events fits well with the multigenic pattern of inheritance expected in HSCR, and further support the role of RET ligands in development of the enteric nervous system.

Amino Acid Sequence↗
PubMed1998

Wilms' tumor and gonadal dysgenesis in a child with the 2q37.1 deletion syndrome.

Here we report Wilms' tumor, gonadal dysgenesis and a bifid uterus in an 18-month-old female with a terminal deletion of the long arm of chromosome 2 [46,XX,del(2)(q37.1)]. Since Wilms' tumor has been previously reported in the 2q37 deletion syndrome, the present observation raises the question of whether a tumor susceptibility gene maps to chromosome 2q37 and suggests giving consideration to the possible occurrence of Wilms' tumor in the course of disease.

Abnormalities, Multiple↗
PubMed1998

Mutation of the MITF gene in albinism-deafness syndrome (Tietz syndrome).

A mother and her son with albinism and sensorineural deafness compatible with Tietz syndrome (MIM 103500) are reported. An in-frame deletion of the MITF gene that is identical at the molecular level to the mouse mi mutant allele has been found in this family. MITF gene mutations account for 20% of Waardenburg syndrome (WS) type II. These data, together with the wide spectrum of mutant alleles reported in mi mice (which have pigmentary disorders), suggest that MITF could be regarded as a candidate gene in various pigmentation disorders in man.

Adult↗
PubMed1998

[Angiomatous and cerulodermic macules: early cutaneous signs of neurofibromatosis type I].

BACKGROUND: Diagnosis of neurofibromatosis type I (NF-1) relies on the NIH consensus conference criteria. However, because of delayed penetrance, they are of limited value in infancy or early childhood. Less frequent signs, namely blue-red and fusco-ceruleus macules, may be clues for diagnosis. CASE REPORTS: We report on two children, aged 2 1/2 and 5, in whom these cutaneous findings were present early in childhood. In addition, they had sufficient criteria for NF1. DISCUSSION: These cutaneous signs, although infrequently reported, are present early in life. Hence they may be useful clues for diagnosis of NF-1 in childhood.

Cafe-au-Lait Spots↗
PubMed1998

[From monogenic to polygenic: model of Hirschsprung disease].

Hirschsprung's disease (HSCR, aganglionic megacolon) is a frequent congenital malformation regarded as a multigenic neurocristopathy. Three susceptibility genes have been recently identified in HSCR, namely the RET proto-oncogene, the endothelin B receptor (EDNRB) gene, and the endothelin 3 (EDN3) gene. RET gene mutations were found in significant proportions of familial (50%) and sporadic (15-20%) HSCR, while homozygosity for EDNRB or EDN3 mutations accounted for the rare HSCR-Waardenburg syndrome (WS) association. More recently, heterozygous EDNRB and EDN3 missense mutations have been reported in isolated HSCR patients. Some of these results were obtained after the identification of mouse genes whose natural or site-directed mutations resulted in megacolon and coat color spotting. There is also conclusive evidence for the involvement of other independent loci in HSCR. In particular, the recent identification of neurotrophic factors acting as RET ligands (GDNF and Neurturin) provide additional candidate genes for HSCR. The dissection of the genetic etiology of HSCR disease may then provide a unique opportunity to distinguish between a polygenic and a genetically heterogeneous disease, thereby helping to understand other complex disorders and congenital malformations hitherto considered as multifactorial in origin. Finally, the study of the molecular bases of HSCR is also a step towards the understanding of developmental genetics of the enteric nervous system giving support to the role of the tyrosine kinase and endothelin-signaling pathways in the development of neural crest-derived enteric neurons in human.

Animals↗
PubMed1997

Differential SP220K expression in renal carcinoma and oncocytoma cells.

SP220K is a newly described serine proteinase which displays guanidinobenzoatase activity in its inactive form and gelatinolytic activity in its active form. SP220K expression was studied in 20 renal clear-cell carcinomas and in a series of renal oncocytomas, a rare benign tumor derived from the kidney tubule epithelium. We provide evidence that SP220K expression, as assessed by guanidinobenzoatase activity, gelatin zymography and Western blot immunodetection, was increased markedly in cancer basolateral membranes compared to kidney cortex controls, whereas no signal was detectable in basolateral membranes from the 5 renal oncocytomas studied. Cytoplasms of carcinoma cells were immunodetected consistently, whereas no expression was seen in oncocytic cells from any of the oncocytomas studied (12/12). Endothelial cells were immunodetected in all 3 tissue types. Our data favor a potential mechanistic relationship between expression of the matrix proteinase SP220K and invasive phenotype in kidney epithelium proliferative processes.

Adenoma, Oxyphilic↗