A second locus (GLC3B) for primary congenital glaucoma (Buphthalmos) maps to the 1p36 region

Primary congenital glaucoma (gene symbol: GLC3) is an ocular disorder that occurs for 0.01-0.04% of blind people. In the majority of familial cases reported so far, this condition is inherited as an autosomal recessive trait. We have recently used a group of 17 GLC3 families with a minimum of two affected offspring and consanguinity in most of the parental generation and mapped the first GLC3 locus (GLC3A) to the 2p21 region. Six families did not show any linkage to the GLC3A locus and thus provided evidence for genetic heterogeneity of this disorder. A total of eight families unlinked to the 2p21 region were used to search for the chromosomal location of the second GLC3 locus. Herein, we describe mapping of a new locus (designated GLC3B) for primary congenital glaucoma to the short arm of chromosome 1 (1p36.2-36.1) that is situated centromeric to the neuroblastoma and Charcot-Marie-Tooth type 2A (CMT2A) loci. A total of 17 DNA markers were genotyped from this region of chromosome 1. Four families showed no recombination with the two markers D1S2834 and D1S402 with a maximum lod score of 4.510 and 4.157 respectively. Pairwise and multipoint linkage analysis and inspection of the haplotypes revealed that the remaining four families are not linked to this part of chromosome 1, thus providing further evidence that at least one more locus for the autosomal recessive form of GLC3 must exist in the genome. Based on the recombination events, the overall linkage map of this region is: tel-D1S1192-D1S1635-D1S1193 - (D1S1597/-D1S489/D1S228)- [GLC3B/D1S2834/D1S402] - (D1S1176/D1S507/D1S407) - D1S2728-(MFAP2/D1S170) - D1S1368 - D1S436- D1S1592-cen.      

46, XY gonadal dysgenesis: new SRY point mutation in two siblings with paternal germ line mosaicism

Stoppa‐Vaucher S, Ayabe T, Paquette J, Patey N, Francoeur D, Vuissoz J‐M, Deladoëy J, Samuels ME, Ogata T, Deal CL. 46, XY gonadal dysgenesis: new SRY point mutation in two siblings with paternal germ line mosaicism. Familial recurrence risks are poorly understood in cases of de novo mutations. In the event of parental germ line mosaicism, recurrence risks can be higher than generally appreciated, with implications for genetic counseling and clinical practice. In the course of treating a female with pubertal delay and hypergonadotropic hypogonadism, we identified a new missense mutation in the SRY gene, leading to somatic feminization of this karyotypically normal XY individual. We tested a younger sister despite a normal onset of puberty, who also possessed an XY karyotype and the same SRY mutation. Imaging studies in the sister revealed an ovarian tumor, which was removed. DNA from the father's blood possessed the wild type SRY sequence, and paternity testing was consistent with the given family structure. A brother was 46, XY with a wild type SRY sequence strongly suggesting paternal Y‐chromosome germline mosaicism for the mutation. In disorders of sexual development (DSDs), early diagnosis is critical for optimal psychological development of the affected patients. In this case, preventive karyotypic screening allowed early diagnosis of a gonadal tumor in the sibling prior to the age of normal puberty. Our results suggest that cytological or molecular diagnosis should be applied for siblings of an affected DSD individual.     

The role of the duodenal microflora as a determinant of persistent diarrhoea

It has been suggested that proliferation of enterobacteriaceae and/or anaerobes in the duodenum of some children with acute diarrhoea determines whether the episode becomes persistent. A review of published studies and the comparison of cultures of duodenal aspirates from Peruvian children with acute and persistent diarrhoea and diarrhoea-free children did not support this hypothesis. Although many children had enterobacteriaceae and/or anaerobes cultured there was no correlation with clinical and nutritional outcome. Age, nutritional status, the environment and the aetiology of the episode were determinants of the duodenal microflora independent of diarrhoea. Culture of the duodenal aspirates did not increase the yield of enteropathogens which were isolated more frequently from stools than from the duodenum. Despite the presence of a single strain or serotype of enterobacteriaceae suggesting that these bacteria were colonizing the duodenum, we were unable to demonstrate any adherence mechanisms in the majority of them. Two often bacteria with no other evidence of virulence caused diarrhoea in the RITARD rabbit model.     

Surgical strategies in very-low-birthweight neonates with necrotizing enterocolitis

Very-low-birthweight (VLBW) neonates are more prone to complications and death than term infants are. In a 15-year period, 19 neonates with VLBW were operated on for necrotizing enterocolitis (NEC). Indications for operation were pneumoperitoneum in 12 and deterioration of general condition in 7. Bowel resection and intestinal diversion was performed in 12, a lateral enterostomy at the site of perforation was created in 5, and 2 neonates with necrosis of the whole bowel underwent an exploratory laparotomy without any further surgical treatment. Surgical complications were found in one-third of the patients. The mortality rate was significantly higher when the ileum was affected. The survival rate was 68%. Prior to 1984 the survival rate was 37% (3/8); subsequently, it has improved to 91% (10/11) as a result of improved intensive therapy.     

External fixation for unstable intra-articular distal radial fractures in women older than 55 years. Acceptable functional end results in the majority of the patients despite significant secondary displacement

Unstable intra-articular distal radial fractures in women older than 55 years were treated by closed reduction and external fixation to achieve the best functional outcome. Sixteen women had radiographic and functional assessment. Despite initial good alignment secondary displacement occurred in 11 patients, probably due to the comminution of the fracture and possibly influenced by osteoporosis. Malunion of the distal radius was seen in two patients and intra-articular incongruity with an intra-articular step exceeding 1 mm was observed in two other patients. The functional outcome was excellent or good in 10 and fair in two patients. Four patients had a poor functional outcome. Two of these patients had a significant loss of reduction, one resulting in a malunion. The other two had an intra-articular incongruity of more than 1 mm. Three of the four patients with a poor functional outcome had clinical signs of reflex sympathetic dystrophy. CONCLUSION: Closed reduction and external fixation of "bad case" severely comminuted unstable distal radial fractures in the elderly may result in an acceptable functional outcome in the majority of the cases, although significant secondary displacement occurred in eleven of the sixteen patients.