Search PubMed⌕ Search

Biomedical subjects

B C Hamel

Publications and source records attributed to B C Hamel.

At least 55 records · Page 3Linked to original sources
PubMed1998

Pfeiffer syndrome type 2: further delineation and review of the literature.

We present 5 unrelated patients, 3 boys and 2 girls, with Pfeiffer syndrome (PS) type 2. They all had cloverleaf skull, severe proptosis, ankylosis of the elbows, broad thumbs and/or broad halluces and variable accompanying anomalies. We review the literature on all subtypes of PS. Most patients with PS type 2 died shortly after birth. Causes of death include pulmonary problems, brain abnormalities, prematurity and post-operative complications. DNA studies were performed in 3 of the 5 patients. Two of them showed a 1036T --> C mutation in the fibroblast growth factor receptor 2 (FGFR2) gene, that was earlier reported in PS and in Crouzon syndrome. Probably most, if not all, PS type 2 cases are caused by a de novo mutation in the FGFR2 gene or in another, yet unidentified gene. To date all type 2 cases have been non-familial. A low recurrence risk for parents can be advised.

Abnormalities, Multiple↗
PubMed1998

The cerebro-costo-mandibular syndrome: seven patients and review of the literature.

We report seven patients with the cerebro-costo-mandibular syndrome, a multiple congenital anomaly syndrome with, as the most distinctive features extreme micrognathia and abnormal rib development. Twice a parent to child transmission was found, compatible with autosomal dominant mode of inheritance. One of our patients presented with absence of the auditory canals and subluxation of the radial head, and another with choanal atresia, findings that have not been published previously. Longterm follow-up of some of the patients is described, and an overview of the literature is given.

Abnormalities, Multiple↗
PubMed1998

Ehlers-Danlos syndrome and type III collagen abnormalities: a variable clinical spectrum.

Ehlers Danlos syndrome (EDS) comprises ten types. EDS IV is the most severe type because of its often lethal complications, such as arterial rupture. EDS IV is caused by an abnormality of collagen type III as a result of mutations in the corresponding gene COL3A1. A collagen type III abnormality is also seen in patients with EDS without the classical severe EDS IV phenotype. We report on 11 patients with type III collagen abnormality and normal collagen V in whom clinically EDS II, III, and IV were diagnosed. There is no correlation between the type of collagen III anomaly and the clinical phenotype. It is concluded that type III collagen abnormality may lead to a phenotypic spectrum and that it does not predict the severity and course of the disease.

Adult↗
PubMed1998

Molecular genetic analysis of the gene encoding the trifunctional enzyme MTHFD (methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, formyltetrahydrofolate synthetase) in patients with neural tube defects.

It is now well recognized that periconceptional folic acid or folic acid containing multivitamin supplementation reduces the risk of neural tube defects (NTDs). Recently we were able to show that homozygosity for a thermolabile variant of the enzyme methylenetetrahydrofolate reductase is associated with an increased risk for spina bifida in patients recruited from the Dutch population. However, this genetic risk factor could not account for all folic acid preventable NTDs. In an attempt to identify additional folate related enzymes that contribute to NTD etiology we now studied the methylenetetrahydrofolate dehydrogenase gene on chromosome 14q24 which encodes a single protein with three catalytic properties important in the folate metabolism. The cDNA sequence of 38 familial and 79 sporadic patients was screened for the presence of mutations by single strand conformation polymorphism (SSCP) analysis followed by sequencing. Two amino acid substitutions were identified. The first one (R293H) was detected in a patient with familial spina bifida and not in 300 control individuals. The mutation was inherited from the unaffected maternal grandmother and was also present in two younger brothers of the index patient, one of them displaying spina bifida occulta and the other being unaffected. The second change turned out to be an amino acid polymorphism (R653Q) that was present in both patients and controls with similar frequencies. Our results so far provide no evidence for a major role of the methylenetetrahydrofolate-dehydrogenase (MTHFD) gene in NTD etiology. However, the identification of a mutation in one family suggests that this gene can act as a risk factor for human NTD.

Aminohydrolases↗
PubMed1998

Localisation of a gene for non-specific X linked mental retardation (MRX46) to Xq25-q26.

We report linkage data on a new large family with non-specific X linked mental retardation (MRX), using 24 polymorphic markers covering the entire X chromosome. We could assign the underlying disease gene, denoted MRX46, to the Xq25-q26 region. MRX46 is tightly linked to the markers DXS8072, HPRT, and DXS294 with a maximum lod score of 5.12 at theta=0. Recombination events were observed with DXS425 in Xq25 and DXS984 at the Xq26-Xq27 boundary, which localises MRX46 to a 20.9 cM (12 Mb) interval. Several X linked mental retardation syndromes have been mapped to the same region of the X chromosome. In addition, the localisation of two MRX genes, MRX27 and MRX35, partially overlaps with the linkage interval obtained for MRX46. Although an extension of the linkage analysis for MRX35 showed only a minimal overlap with MRX46, it cannot be excluded that the same gene is involved in several of these MRX disorders. On the other hand, given the considerable genetic heterogeneity in MRX, one should be extremely cautious in using interfamilial linkage data to narrow down the localisation of MRX genes. Therefore, unless the underlying gene(s) is characterised by the analysis of candidate genes, MRX46 can be considered a new independent MRX locus.

Adult↗
PubMed1997

[Ehlers-Danlos syndrome IV: phenotype variation].

In three female patients, 20, 4 and 29 years of age, Ehlers-Danlos syndrome (EDS) IV was diagnosed on the basis of a deficiency of collagen III with among other things a hyperextensible skin and joints and easy bruising. Severity of symptoms varies considerably per patient. EDS comprises 10 types. Type IV is the most severe type because of its often lethal complications like arterial rupture. Deficiency of collagen III is also seen in EDS patients without the classical severe EDS IV phenotype. It is suggested to restrict collagen III analysis to patients who are suspected of having classical EDS IV.

Adult↗
PubMed1997

Two sibs with chorioretinal dystrophy, hypogonadotrophic hypogonadism, and cerebellar ataxia: Boucher-Neuhäuser syndrome.

We describe two sibs with chorioretinal dystrophy, hypogonadotrophic hypogonadism, and cerebellar ataxia, Boucher-Neuhäuser syndrome, a rare but distinct pleiotropic single gene disorder with an autosomal recessive pattern of inheritance. The cases presented illustrate that this syndrome is still poorly recognised. We provide a review and analysis of previously reported cases and the differential diagnosis, which might aid in the identification of additional cases.

Adult↗
PubMed1997

[Cleft lip and palate: thoughts about associated anomalies].

During two years all new patients referred to the cleft palate team in Nijmegen, were examined by a clinical dentist, to evaluate the occurrence of associated anomalies or syndromes. In 33% of the patients with all types of clefts associated anomalies were found. A percentage of 56% was found for cleft palate only, and of 14% for cleft lip (palate). It is important to make a classifying diagnosis of these associated anomalies because they may have important implications for recurrence risks and prognosis. The percentage of associated anomalies is the highest in the group of patients with cleft palate only or submucous clefts. Therefore, the dentists have to be aware of the presence of submucous clefts and their consequences.

Cleft Lip↗
PubMed1997

Heminasal aplasia: a case report and review of the literature of the last 25 years.

We report a child with right-sided heminasal aplasia in combination with anomalies of the right eye and maxilla. Unilateral aplasia of the nose is a rare congenital malformation. It is often associated with other malformations of the facial region, including abnormalities of the eye and lacrimal system, proboscis lateralis, and facial bone malformations. The eye anomalies in our patient consisted of microphthalmia with blepharophimosis and coloboma of the iris, retina and upper eyelid. Also hypoplasia of the lacrimal apparatus and right maxilla, and a rudimentary alveolar cleft on the same side were present. The embryological development of the midface can explain this association of anomalies.

Abnormalities, Multiple↗
PubMed1996

Prevalence of familial mild hyperhomocysteinemia.

Previous studies have shown that elevated basal homocysteine levels are correlated among family members of patients with coronary vascular disease and juvenile venous thrombosis. This suggests the possibility of the presence of inherited basal mild hyperhomocysteinemia (mHH). We studied homocysteine levels, fasting as well as after methionine load, among 96 family members of 21 post-load hyperhomocysteinemic vascular index patients, i.e. 6 parents, 27 offspring, 38 siblings, 19 uncles and aunts and 6 cousins. In 15 out of 21 screened families post-load mHH was established in at least one family member. Fasting and post-load mHH was observed in 19 out of 89 (21%) screened family members (fasting homocysteine levels not measured in seven family members), and 31 out of 96 screened family members (32%), respectively. In 40% of all family members, post-load mHH was not accompanied by fasting mHH. We conclude that both fasting and post-load mHH seems to be inherited in the majority of hyperhomocysteinemic vascular patients.

Adult↗
PubMed1996

A gene for nonspecific X-linked mental retardation (MRX41) is located in the distal segment of Xq28.

We report on a family in which nonsyndromal mild to moderate mental retardation segregates as an X-linked trait (MRX41). Two point linkage analysis demonstrated linkage between the disorder and marker DXS3 in Xq21.33 with a lod score of 2.56 at theta = 0.0 and marker DXS1108 in Xq28 with a lod score of 3.82 at theta = 0.0. Multipoint linkage analysis showed that the odds for a location of the gene in Xq28 vs Xq21.33 are 100:1. This is the fourth family with non-specific X-linked mental retardation with Xq28-qter as the most likely gene localization.

Chromosome Mapping↗
PubMed1996

Familial X-linked mental retardation and isolated growth hormone deficiency: clinical and molecular findings.

We report on several members of a family with varying degrees of X-linked mental retardation (XLMR), isolated growth hormone deficiency (IGHD), and infantile behaviour but without other consistent phenotypic abnormalities. Male patients continued to grow until well into their twenties and reached a height ranging from 135 to 159 cm. Except one, all female carriers were mentally normal; their adult height ranged from 159 to 168 cm. By linkage studies we have assigned the underlying genetic defect to the Xq24-q27.3 region, with a maximum lod score of Z = 3.26 at theta = 0.0 for the DXS294 locus. The XLMR-IGHD phenotype in these patients may be due to pleiotropic effects of a single gene or it may represent a contiguous gene syndrome.

Adult↗
PubMed1996

Genetic counselling and prenatal diagnosis in disorders of the mitochondrial energy metabolism.

Point mutations in mitochondrial DNA, as found in MELAS, MERRF, NARP and other syndromes, are inherited via the maternal lineage. Genetic counselling can be beneficial, but prenatal diagnosis is not advantageous in these syndromes. Empirical data about the recurrence risk can be applied in Leber disease (LHON). Mitochondrial disorders not associated with a point mutation have a sporadic nature (large deletions/duplications in mitochondrial DNA) or are transmitted according to Mendelian laws. Autosomal dominant inheritance is likely to be found in disorders with depletion of mitochondrial DNA. X-linked mode of inheritance is seen in Menkes disease, Barth syndrome, and in deficiencies of the E1 alpha subunit of the pyruvate dehydrogenase complex. Mutation analysis or linkage studies can be applied for carrier detection and prenatal diagnosis in these three types of mitochondriopathies. The majority of the disorders with a disturbed mitochondrial energy metabolism are likely inherited in an autosomal recessive mode. Prenatal diagnosis can be performed in the cases of cytochrome c oxidase and NADH dehydrogenase deficiencies in chorionic villi in selected families.

DNA, Mitochondrial↗
PubMed1996

Additional congenital defects in anorectal malformations.

UNLABELLED: From 1974 until 1995 a total of 264 (141 male, 123 female) patients born with an anorectal malformation (ARM) were referred to the University Hospital Nijmegen in the Netherlands. All additional congenital defects (ACDs) were registered. Special attention was paid to whether the ACDs take part in associations, syndromes, or sequences. One or more ACDs were observed in 67% of the patients. In decreasing order the defects concerned the uro-genital tract (43%), skeleton (38%), gastrointestinal tract (24%), circulation (21%), extremities (16%), face (16%), central nervous system (15%), respiratory tract (5%), and remaining defects (5%). Associations were observed in 49% of the patients mostly (in 44%) the Vertebral, Anorectal, Cardial, Tracheo-Esophageal, Renal and Limb association. In 5% of the patients syndromes were recognized. Sequences were seen in 2% of the patients. Remarkable is the combination of trisomy 21 and ARM without a fistula. The combination of ARM and the Zellweger syndrome has not been reported before. CONCLUSION: Almost all combinations of ARM and ACDs can be classified as an association, syndrome or sequence. ARM-causing agents affect males and females in equal numbers but lead to different expression in the sexes. The origin of the Omphalocele, Extrophia of the bladder, Imperforate anus, Sacral anomalies complex probably differs from that of other forms of ARM.

Abnormalities, Multiple↗
PubMed1996

Localization of the gene (or genes) for a syndrome with X-linked mental retardation, ataxia, weakness, hearing impairment, loss of vision and a fatal course in early childhood.

Linkage analysis is described in a family with X-linked mental retardation, ataxia, weakness, floppiness, delayed motor development, absence of deep tendon reflexes, hearing impairment and loss of vision (MIM no. 301835). The disease has a fatal course due to the susceptibility of the patients to infections, especially of the respiratory tract. Clinical signs indicate impairment of the posterior columns, peripheral motor and sensory neurons and the second and eighth cranial nerves and/or their nuclei. The involvement of the posterior columns of the spinal cord is further suggested by the almost complete absence of myelinated fibers therein. We localized the responsible gene(s) to Xq21.33-q24 between DXS1231 and DXS1001 with a maximum lod score of 6.97. The proteolipid protein gene, which codes for two myelin proteins of the central nervous system and is located in this region, was considered as a candidate gene for this disorder. However, no mutations were found in the protein-coding part of this gene.

Ataxia↗