Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2.

A gene mutated in Charcot-Marie-Tooth disease type 4B (CMT4B), an autosomal recessive demyelinating neuropathy with myelin outfoldings, has been mapped on chromosome 11q22. Using a positional-cloning strategy, we identified in unrelated CMT4B patients mutations occurring in the gene MTMR2, encoding myotubularin-related protein-2, a dual specificity phosphatase (DSP).

Autosomal-recessive forms of demyelinating Charcot-Marie-Tooth disease.

Autosomal-recessive forms of Charcot-Marie-Tooth (ARCMT) account for less than 10% of the families in the European CMT population but are more frequent in the Mediterranean basin and the Middle East because of more widespread consanguinity. Until now, demyelinating ARCMT was more extensively studied at the genetic level than the axonal form. Since 1999, the number of localized or identified genes responsible for demyelinating ARCMT has greatly increased. Eight genes, EGR2, GDAP1, KIAA1985, MTMR2, MTMR13, NDRG1, PRX, and CTDP1, have been identified and two new loci mapped to chromosomes 10q23 and 12p11-q13. In this review, we will focus on the particular clinical and/or neuropathological features of the phenotype caused by mutations in each of these genes, which might guide molecular diagnosis.

Viral pathogens and clinical manifestations associated with acute lower respiratory tract infections in children of the Sudan.

BACKGROUND: Incomplete knowledge regarding the viral agents causing respiratory infections in children living in developing countries impedes diagnosis and management of patients. OBJECTIVES: To assess the role of viral pathogens in Sudanese children presenting with acute lower respiratory tract infections (ALRI). STUDY DESIGN: The study population consisted of patients presenting with ALRI at the Children's Emergency Hospital in Khartoum during 2 periods (December 1987 to April 1988 and September 1990 to March 1991). Identification of viral infections was based an antigen detection by immunofluorescence and enzyme-linked immunosorbent assay (ELISA) on nasopharyngeal secretions and/or serology. RESULTS: After exclusion of children with measles, 102 and 111 children, respectively, were prospectively enrolled in the study during the 2 periods. Their ages ranged between one mouth and 14 years (mean 2.0 years). Radiologic pulmonary infiltrations were detected in 135 (66%) of the 206 patients who had chest radiographs, whereas 7 (3%) showed lobar pneumonia. The case fatality rate was 2.3%. Of 83 virus infections detected, 79 were in children < years and consisted mainly of respiratory syncytial virus (RSV, 28%), followed by parainfluenza (7%), adenovirus (5%) and influenza A (2%). Infiltrates on radiographs were significantly less often found in virus-infected cases than in ALRI-cases with negative virus tests. CONCLUSIONS: RSV predominantly infected young infants (

Genetic refinement and physical mapping of the CMT4B gene on chromosome 11q22.

Charcot-Marie-Tooth disease type 4B (CMT4B) is a demyelinating autosomal recessive motor and sensory neuropathy characterized by focally folded myelin sheaths in the peripheral nerve. We recently mapped the CMT4B gene to a 5-cM interval on chromosome 11q22, using homozygosity mapping and haplotype sharing analysis on a large inbred pedigree. In the present study, we report the construction of a YAC-based transcript map across the 5-cM critical region, including 26 YACs, 35 STSs, and 52 ESTs. Furthermore, using 15 additional physically ordered microsatellite markers from the 11q22 region on the original inbred family, we were able to narrow the critical interval for the gene to 2 Mb, which is now flanked by markers D11S1757 and CHLC-GATA3B05. Finally, after computer analysis of the 33 ESTs assigned to the 2-Mb interval, we demonstrated that 21 different transcripts as well as 3 known genes might represent potential candidates for the disease.