EPI Update, June 5, 2015

Weekly newsletter for Center For Acute Disease Epidemiology of Iowa Department of Public Health.

EPI Update, June 12, 2015

Weekly newsletter for Center For Acute Disease Epidemiology of Iowa Department of Public Health.

EPI Update, June 19, 2015

Weekly newsletter for Center For Acute Disease Epidemiology of Iowa Department of Public Health.

Multicentric carpotarsal osteolysis is caused by mutations clustering in the amino-terminal transcriptional activation domain of MAFB.

Multicentric carpotarsal osteolysis (MCTO) is a rare skeletal dysplasia characterized by aggressive osteolysis, particularly affecting the carpal and tarsal bones, and is frequently associated with progressive renal failure. Using exome capture and next-generation sequencing in five unrelated simplex cases of MCTO, we identified previously unreported missense mutations clustering within a 51 base pair region of the single exon of MAFB, validated by Sanger sequencing. A further six unrelated simplex cases with MCTO were also heterozygous for previously unreported mutations within this same region, as were affected members of two families with autosomal-dominant MCTO. MAFB encodes a transcription factor that negatively regulates RANKL-induced osteoclastogenesis and is essential for normal renal development. Identification of this gene paves the way for development of novel therapeutic approaches for this crippling disease and provides insight into normal bone and kidney development.

Mutations in tubulin genes are frequent causes of various foetal malformations of cortical development including microlissencephaly.

Complex cortical malformations associated with mutations in tubulin genes are commonly referred to as "Tubulinopathies". To further characterize the mutation frequency and phenotypes associated with tubulin mutations, we studied a cohort of 60 foetal cases. Twenty-six tubulin mutations were identified, of which TUBA1A mutations were the most prevalent (19 cases), followed by TUBB2B (6 cases) and TUBB3 (one case). Three subtypes clearly emerged. The most frequent (n = 13) was microlissencephaly with corpus callosum agenesis, severely hypoplastic brainstem and cerebellum. The cortical plate was either absent (6/13), with a 2-3 layered pattern (5/13) or less frequently thickened (2/13), often associated with neuroglial overmigration (4/13). All cases had voluminous germinal zones and ganglionic eminences. The second subtype was lissencephaly (n = 7), either classical (4/7) or associated with cerebellar hypoplasia (3/7) with corpus callosum agenesis (6/7). All foetuses with lissencephaly and cerebellar hypoplasia carried distinct TUBA1A mutations, while those with classical lissencephaly harbored recurrent mutations in TUBA1A (3 cases) or TUBB2B (1 case). The third group was polymicrogyria-like cortical dysplasia (n = 6), consisting of asymmetric multifocal or generalized polymicrogyria with inconstant corpus callosum agenesis (4/6) and hypoplastic brainstem and cerebellum (3/6). Polymicrogyria was either unlayered or 4-layered with neuronal heterotopias (5/6) and occasional focal neuroglial overmigration (2/6). Three had TUBA1A mutations and 3 TUBB2B mutations. Foetal TUBA1A tubulinopathies most often consist in microlissencephaly or classical lissencephaly with corpus callosum agenesis, but polymicrogyria may also occur. Conversely, TUBB2B mutations are responsible for either polymicrogyria (4/6) or microlissencephaly (2/6).

EPI Update, August 21, 2015

Weekly newsletter for Center For Acute Disease Epidemiology of Iowa Department of Public Health.

EPI Update, August 28, 2015

Weekly newsletter for Center For Acute Disease Epidemiology of Iowa Department of Public Health.

EPI Update, August 7, 2015

Weekly newsletter for Center For Acute Disease Epidemiology of Iowa Department of Public Health.

EPI Update, June 26, 2015

Weekly newsletter for Center For Acute Disease Epidemiology of Iowa Department of Public Health.

EPI Update, July 24, 2015

Weekly newsletter for Center For Acute Disease Epidemiology of Iowa Department of Public Health.

EPI Update, July 10, 2015

Weekly newsletter for Center For Acute Disease Epidemiology of Iowa Department of Public Health.

EPI Update, July 17, 2015

Weekly newsletter for Center For Acute Disease Epidemiology of Iowa Department of Public Health.

EPI Update, July 31, 2015

Weekly newsletter for Center For Acute Disease Epidemiology of Iowa Department of Public Health.

EPI Update, August 14, 2015

Weekly newsletter for Center For Acute Disease Epidemiology of Iowa Department of Public Health.

EPI Update, September 4, 2015

Weekly newsletter for Center For Acute Disease Epidemiology of Iowa Department of Public Health.