The KLHL40 c.1516A>C is a Chinese-specific founder mutation causing nemaline myopathy 8: Report of six patients with pre- and postnatal phenotypes.

BACKGROUND: Autosomal recessive or compound heterozygous mutations in KLHL40 cause nemaline myopathy 8, which is one of the most severe forms of nemaline myopathy. The KLHL40 c.1516A>C variant has recently been reported as a founder mutation in southern Chinese. METHODS: We report six cases of nemaline myopathy 8 which involves the c.1516A>C variant, from five unrelated families of non-consanguineous southern Chinese. The pre- and postnatal phenotypes of these cases were reviewed with emphasis on prenatal clinical features. Genetic testing for the founder mutation was performed on three patients with homozygous mutations. RESULTS: Common prenatal features included reduced fetal movement, polyhydramnios, breech presentation, and clubfeet. Two pregnancies were terminated. Four live-born patients had postnatal features typical of nemaline myopathy 8. The length of survival ranged from 49 days to 17 months, with respiratory failure and infections being the principal causes of death. Haplotype analysis in three patients with homozygous mutation showed a shared haplotype block of 1.1727 cM spanning over the c.1516A>C variant, suggesting it is a southern Chinese-specific founder mutation. CONCLUSION: Analysis of the KLHL40 c.1516A>C variant should be considered in prenatal diagnosis of Chinese pregnant patients with suspected congenital neuromuscular disorders or with significant family history of congenital myopathies.

Intensive care unit admission of obstetric cases: a single centre experience with contemporary update.

OBJECTIVES. To review the characteristics of a series of obstetric patients admitted to the intensive care unit in a regional hospital in 2006-2010, to compare them with those of a similar series reported from the same hospital in 1989-1995 and a series reported from another regional hospital in 1998-2007. DESIGN. Retrospective case series. SETTING. A regional hospital in Hong Kong. PATIENTS. Obstetric patients admitted to the Intensive Care Unit of Kwong Wah Hospital from 1 January 2006 to 31 December 2010. RESULTS. From 2006 to 2010, there were 67 such patients admitted to the intensive care unit (0.23% of total maternities and 2.34% of total intensive care unit admission), which was a higher incidence than reported in two other local studies. As in the latter studies, the majority were admitted postpartum (n=65, 97%), with postpartum haemorrhage (n=39, 58%) being the commonest cause followed by pre-eclampsia/eclampsia (n=17, 25%). In the current study, significantly more patients had had elective caesarean sections for placenta praevia but fewer had had a hysterectomy. The duration of intensive care unit stay was shorter (mean, 1.8 days) with fewer invasive procedures performed than in the two previous studies, but maternal and neonatal mortality was similar (3% and 6%, respectively). CONCLUSION. Postpartum haemorrhage and pregnancy-induced hypertension were still the most common reasons for intensive care unit admission. There was an increasing trend of intensive care unit admissions following elective caesarean section for placenta praevia and for early aggressive intervention of pre-eclampsia. Maternal mortality remained low but had not decreased. The intensive care unit admission rate by itself might not be a helpful indicator of obstetric performance.