Exome sequencing reveals three homozygous missense variants in SNRPA in two sisters with syndromic intellectual disability.

Splicing-related gene mutations might affect the expression of a single gene or multiple genes and cause clinically heterogeneous diseases. With the advent of next-generation sequencing, several splicing gene mutations have been exposed, yet most major spliceosome genes have no reports of germline mutations and therefore, their effects are largely unknown. We describe the previously unreported concurrence of intellectual disability, short stature, poor speech, and minor craniofacial and hand anomalies in 2 female siblings with 3 homozygous missense variants in SNRPA (a component of the U1 small nuclear ribonucleoprotein complex) characterized by homozygosity mapping and whole exome sequencing. Combined, c.97A>G, c.98T>C, and c.100T>A, in exon 2 of SNRPA lead to p.Ile33Ala and p.Phe34Ile exchanges, which were predicted in silico to be deleterious. Although both patients exhibited some clinical features seen in other spliceosomal disorders, their complete clinical phenotype appears to be rather uncommon, a finding that may further support the notion that mutations in components of the major spliceosome do not strictly lead to the same syndromes/phenotypes.

Outcome of hip fractures among elderly subjects.

This paper reports a retrospective study (1979-1995) on 200 patients (154 women and 46 men), 50-101 years old, who received medical attention because of unilateral hip fracture. Nine women and four men fractured twice. In 75% of women and 90% of men, surgery was carried out between one and five days after fracture. A non significant greater proportion of women (14/154) than men (6/46) died in the first year after injury (chi 2 = 3.459, P = 0.062). Survival was assessed using Cox proportional hazards model. Survival was a function of age (P = 0.000) and sex (P = 0.008). After adjustment to a common mean age (79 years), the median survivals for men and women were 3.9 and 8.4 years, respectively. Controlled concurrent life-threatening diseases, the kind of fracture [medial (subcapital and transcervical) or lateral (inter- and subtrochanteric)] and the type of prosthesis (total/partial articulation replacement) had no significant impact on survival. No differences in evolution were observed: 80% returned to their ambulatory status before injury, 8.5% required walking aids and 5.5% could not walk. The overall information afforded by this study suggests that with worldwide improvement of hip fracture outcome, the cost/effectiveness of surgical treatment of hip fracture may become, from the standpoint of public health investment, a favorable alternative with respect to cost/effectiveness of prevention-treatment measures.