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Biomedical subjects

M A Patton

Publications and source records attributed to M A Patton.

At least 55 records · Page 3Linked to original sources
PubMed1997

Hirschsprung's disease in Oman.

The incidence of Hirschsprung's disease (HD) was studied retrospectively in Oman using hospital-based data. In Oman there is a single pediatric surgery unit where a register has been kept from 1989 to 1994, and because all cases are referred to this unit, a national survey could be carried out. There were 85 children with HD born between 1989 and 1994, and during the period there were 261,000 livebirths among Omani nationals. The population frequency in Oman is 1 in 3,070 (0.3/1,000). Eighty percent of cases presented in the first 6 months. The incidence in different regions and within different tribes of Oman was also studied. The highest frequency (1 in 1,800) is in the North Sharqiya region. There was not a significant seasonal influence in spite of the very high temperatures seen in the desert summer. The ratio of male to female cases was 2.9:1 overall, but less for longer-segment involvement. The consanguinity rate (first and second cousins) was 75%, which is higher than the level of consanguinity in the Omani population. Down's syndrome was observed in nine cases (11%), and a variety of other malformations were seen, including piebaldism, deafness, and HD in two sibships.

Abnormalities, Multiple↗
PubMed1997

The X-linked gene G4.5 is responsible for different infantile dilated cardiomyopathies.

Barth syndrome (BTHS) is an X-linked disorder characterized clinically by the associated features of cardiac and skeletal myopathy, short stature, and neutropenia. The clinical manifestations of the disease are, in general, quite variable, but cardiac failure as a consequence of cardiac dilatation and hypertrophy is a constant finding and is the most common cause of death in the first months of life. X-linked cardiomyopathies with clinical manifestations similar to BTHS have been reported, and it has been proposed that they may be allelic. We have recently identified the gene responsible for BTHS, in one of the Xq28 genes, G4.5. In this paper we report the sequence analysis of 11 additional familial cases: 8 were diagnosed as possibly affected with BTHS, and 3 were affected with X-linked dilated cardiomyopathies. Mutations in the G4.5 gene were found in nine of the patients analyzed. The molecular studies have linked together what were formerly considered different conditions and have shown that the G4.5 gene is responsible for BTHS (OMIM 302060), X-linked endocardial fibroelastosis (OMIM 305300), and severe X-linked cardiomyopathy (OMIM 300069). Our results also suggest that very severe phenotypes may be associated with null mutations in the gene, whereas mutations in alternative portions or missense mutations may give a "less severe" phenotype.

Abnormalities, Multiple↗
PubMed1997

Osteogenesis imperfecta with arthrogryposis multiplex congenita (Bruck syndrome)--evidence for possible autosomal recessive inheritance.

We report a son and a daughter of a first cousin Pakistani marriage who both have osteogenesis imperfecta and the son in addition has arthrogryposis multiplex congenita. Bruck [(1897): Dtsch Med Wochenschr 23: 152-155] first reported the case of a boy who had multiple fractures and joint ankylosis, subsequently only one sibship with three affected cases and seven sporadic cases have been reported to our knowledge. On the basis of consanguinity this suggests that the association of osteogenesis imperfecta and arthrogryposis multiplex congenita is inherited in this family as an autosomal recessive condition with variable expression.

Arthrogryposis↗
PubMed1997

Agenesis of the corpus callosum in Turner syndrome with ring X.

An 8-year-old girl with Turner syndrome and 45,X/46,X,r(X) mosaicism was found to have agenesis of the corpus callosum and various other characteristics including 'kabuki makeup' facial features and mild learning disability. Only two other cases of Turner syndrome associated with agenesis of the corpus callosum have been reported, both in patients with a 45,X karyotype. In both of those patients the constellation of signs differed from those of the present patient in a number of ways. It remains to be confirmed whether there is a higher incidence of CNS malformation in girls who have Turner syndrome with a ring X than has been reported for girls with Turner syndrome in general.

Agenesis of Corpus Callosum↗
PubMed1996

Cobblestone lissencephaly with normal eyes and muscle.

Cobblestone lissencephaly is the characteristic brain malformation observed in Fukuyama congenital muscular dystrophy (FCMD), muscle-eye-brain disease (MEB), and Walker-Warburg syndrome (WWS). The diagnostic criteria for all three require the presence of congenital muscular dystrophy, and criteria for MEB and WWS require retinal abnormalities. We report three patients from two consanguineous families of Middle Eastern origin with cobblestone lissencephaly but no abnormalities of the eyes or muscle. Based on the current diagnostic criteria for the cobblestone lissencephaly syndromes, this disorder must be classified separately from the others, but it may well be allelic to MEB and WWS. Linkage studies have excluded the gene for this disorder from the region of the FCMD gene on chromosome 9q31-32.

Adolescent↗
PubMed1996

The short-term effects of growth hormone therapy on height velocity and cardiac ventricular wall thickness in children with Noonan's syndrome.

Noonan's syndrome (NS) is associated with short stature and cardiac defects. Small studies reported linear growth increases with recombinant human GH (rhGH) therapy, but also raised concerns related to the anabolic effects of rhGH and the possible progression of ventricular hypertrophy. We report a multicenter study examining the efficacy and safety of rhGH (4 IU/m2.day, sc) in children with NS. Entry criteria were: NS confirmed by single observer, height SD score less than -2(UK Height Standards 1990), prepubertal, and normal maximal left ventricular (LV) wall thickness less than 1 cm by 2-dimensional echocardiography. Thirty subjects were recruited (19 males and 11 females), aged 8.9 +/- 0.5 yr (range, 4.8-13.7 yr). Growth was monitored for 12 months before and at 3-month intervals during therapy. Measurements of maximal LV wall thickness were taken at 0 and 12 months. Serum insulin-like growth factor I(IGF-I), IGF-II, and IGF-binding protein-3 levels were determined at 0, 3, 6, 9, and 12 months. Ten subjects with NS (4 females and 6 males), aged 8.8 +/- 0.7 yr (range, 6.3-11.8 yr), were monitored over the same period as a comparison group. In the treatment group, 27 subjects completed 12 months of therapy. Height SD score increased from -3.01 +/- 0.10 to -2.36 +/- 0.10 (P < 0.0001) after 12 months; height velocity (HV) increased from 4.9 +/- 0.2 to 8.9 +/- 0.3 cm/yr at 6 months and 8.1 +/- 0.4 cm/yr (P < 0.0001) from 6-12 months. The HV SD score increased from -0.7 +/- 0.15 to +2.42 +/- 0.32 over 12 months (P < 0.0001). The increase in HV was more than 2 cm/yr in 24 patients. IGF-I increased from 121 +/- 13 to 240 +/- 22 micrograms/L at 12 months (P < 0.0001), and IGF-binding protein-3 increased from 2.65 +/- 0.20 to 4.01 +/- 0.42 mg/L at 12 months (P = 0.0009). In the comparison group, there was no change in height SD score (-2.03 +/- 0.19), HV (4.4 +/- 0.24 CM/yr), or HV SD score (- 1.08 +/- 0.21). There was no increase in mean maximal LV wall thickness during the study in either the treatment group (12 month values were 0.63 +/- 0.02 cm at the mitral valve level and 0.66 +/- 0.02 cm at the papillary muscle level) or in the comparison group (0.63 +/- 0.04 cm at the mitral valve level and 0.61 +/- 0.03 cm at the papillary muscle level). In conclusion, rhGH was effective in 24 of the treated patients; these subjects achieved a significant increase in height SD score and HV over 1 yr. Abnormal anabolic effects of rhGH on myocardial thickness were not confirmed, and no patient developed features of hypertrophic cardiomyopathy.

Adolescent↗
PubMed1995

Familial microtia with meatal atresia and conductive deafness in five generations.

We describe a large family with congenital microtia, auditory meatal atresia and conductive deafness. The pedigree suggests autosomal dominant inheritance with variable expression and low penetrance. The literature is also reviewed to describe the inheritance pattern and clinical spectrum noted in this rare syndrome so far. The family is unique because the set of otologic anomalies in five generations was associated with renal cysts in one of the affected members, suggesting that this oto-renal (OR) syndrome may represent a variable expression of the branchio-oto-renal (BOR) syndrome. However, the probability is that this dominant malformation syndrome is a distinct entity.

Child↗
PubMed1995

Floating-Harbor syndrome: description of a further patient, review of the literature, and suggestion of autosomal dominant inheritance.

UNLABELLED: The Floating-Harbor syndrome is a growth retardation syndrome with delayed bone age, speech development, and typical facial features. The face is triangular with deep-set eyes, long eyelashes, bulbous nose, wide columella, short philtrum, and thin lips. We present an additional patient and review 16 cases from the literature. The possible phenotype in the patient's mother suggests a dominant mode of inheritance for the syndrome. CONCLUSION: The Floating Harbor syndrome is a growth deficiency syndrome characterized by proportionate short stature, characteristic face and delayed speech development. Inheritance is possibly autosomal dominant.

Age Determination by Skeleton↗
PubMed1994

Small terminal deletions of the long arm of chromosome 2: two new cases.

We report on 2 girls with small de novo terminal deletions of the long arm of chromosome 2 and breakpoints within q37. Four cases with similar or more extensive deletions have been previously reported in full. Hypotonia and psychomotor retardation were the only manifestations common to all 6 cases. The phenotype associated with small terminal 2q deletions is variable and clearly not always as mild as indicated in previous reports. The abnormality may also be more common than has been assumed.

Child↗
PubMed1994

Mapping a gene for Noonan syndrome to the long arm of chromosome 12.

Noonan syndrome is characterized by typical facies, short stature and congenital cardiac defects. Approximately half of all cases are sporadic, but autosomal dominant inheritance with variable expression is well established. We have performed a genome-wide linkage analysis in a large Dutch kindred with autosomal dominant Noonan syndrome, and localized the Noonan syndrome gene to chromosome 12 (Zmax = 4.04 at 0 = 0.0). Linkage analysis using chromosome 12 markers in 20 smaller, two-generation families gave Zmax = 2.89 at 0 = 0.07, but haplotype analysis showed non-linkage in one family. These data imply that a gene for Noonan syndrome is located on chromosome 12q, between D12S84 and D12S366.

Chromosome Mapping↗
PubMed1994

Genital tract function in men with Noonan syndrome.

In order to study the pattern of male fertility in Noonan syndrome, and its potential implications for genetic counselling, the genital tract function was studied in 11 adult males with Noonan syndrome. Bilateral testicular maldescent occurred in six. The mean testicular volume was 21 (SD 4) ml. The stretched flaccid penile length was 11.4 (SD 1.2) cm. Puberty was delayed in three. Four of the men had fathered children. The LH and testosterone levels were essentially normal in all men, while the FSH levels were grossly raised in the group with testicular maldescent, with the exception of one man. Semen samples were obtained from five men, and azoospermia or oligozoospermia was present in four of them. Sexual function is not affected in men with Noonan syndrome, but the onset of sexual activity was delayed in men with late onset of puberty. Bilateral testicular maldescent appears to be the main factor contributing to impairment of fertility in men with Noonan syndrome.

Adolescent↗
PubMed1994

Non-Mendelian transmission in a human developmental disorder: split hand/split foot.

The study of Mendelian disorders that do not meet some Mendelian expectations has led to an increased understanding of such previously obscure genetic phenomena as anticipation. Split hand/split foot (SHSF), a human developmental malformation, demonstrates such distinctive genetic features as reduced penetrance and variable expressivity. In this study, new pedigrees with defined ascertainment confirm the existence of non-Mendelian transmission characterized by the overtransmission of SHSF from affected fathers to sons.

Fathers↗
PubMed1994

Fine mapping of the autosomal dominant split hand/split foot locus on chromosome 7, band q21.3-q22.1.

Split hand/split foot (SHFD) is a human developmental defect characterized by missing digits, fusion of remaining digits, and a deep median cleft in the hands and feet. Cytogenetic studies of deletions and translocations associated with this disorder have indicated that an autosomal dominant split hand/split foot locus (gene SHFD1) maps to 7q21-q22. To characterize the SHFD1 locus, somatic cell hybrid lines were constructed from cytogenetically abnormal individuals with SHFD. Molecular analysis resulted in the localization of 93 DNA markers to one of 10 intervals surrounding the SHFD1 locus. The translocation breakpoints in four SHFD patients were encompassed by the smallest region of overlap among the SHfD-associated deletions. The order of DNA markers in the SHFD1 critical region has been defined as PON-D7S812-SHFD1-D7S811-ASNS. One DNA marker, D7S811, detected altered restriction enzyme fragments in three patients with translocations when examined by pulsed-field gel electrophoresis (PFGE). These data map SHFD1, a gene that is crucial for human limb differentiation, to a small interval in the q21.3-q22.1 region of human chromosome 7.

Adult↗
PubMed1994

Blood lead concentrations in hereditary hemochromatosis.

We postulated that patients with hereditary hemochromatosis (HH) absorb increased quantities of lead, as do iron-deficient subjects. To test this hypothesis, whole blood lead concentration ([blood Pb]) was quantified by atomic absorption spectrometry in HH homozygotes (n = 44), obligate heterozygotes (n = 19), normal control subjects (n = 33), and abnormal controls, with transfusion-induced iron overload (n = 8). HH homozygotes had higher [blood Pb] than did normal control subjects (5.6 +/- 0.6 microgram/dl vs 3.6 +/- 0.5 microgram/dl; p < 0.005); significantly increased mean [blood Pb] was observed in both male and female homozygotes. In heterozygotes, the mean [blood Pb] 4.1 +/- 0.5 microgram/dl) was intermediate between that of homozygotes and normal control subjects. The mean [blood Pb] of subjects with transfusion-induced iron overload (22 +/- 0.6 microgram/dl) did not differ significantly from that of normal controls. The findings in homozygotes could to be related to age, serum ferritin concentration, presence or absence of iron loading, or the extent of therapeutic phlebotomy. Lead exposure in all of our subjects was due primarily to ambient sources. Analysis of our data, when using a mathematical biokinetic model of human lead metabolism, suggests that the most likely explanation for our findings is that homozygotes (and, to a lesser extent, heterozygotes) absorb increased quantities of lead, a conclusion that corresponds to the increased absorption of iron and cobalt previously documented in homozygotes.

Adolescent↗