Severe Charcot-Marie-Tooth neuropathy type 1A with 1-base pair deletion and frameshift mutation in the peripheral myelin protein 22 gene.

A 27-year-old man with negative family history and both parents with normal neurological evaluation and motor nerve conduction velocities (MNCVs) showed onset of severe weakness of feet at 4 years of age. Subsequently he developed left equinovarus deformity, thoracic scoliosis, ulnar nerve enlargement, areflexia, distal hypesthesia and slowing of MNCVs for median and ulnar nerves (15-25 m/sec). Molecular genetic studies showed deletion of one nucleotide (G330) (codon 94) in exon 3 of the PMP22 gene associated with frameshift mutation.

Dejerine-Sottas neuropathy in mother and son with same point mutation of PMP22 gene.

We studied a 25-year-old black woman with healthy parents and her 2-year, 11-month-old son. Her motor development was delayed and she started to walk with support when she was 6 years old. She never walked independently and had always used a wheelchair.

Autosomal dominant Charcot-Marie-Tooth axonal neuropathy mapped on chromosome 7p (CMT2D).

Clinical, electrophysiological and genetic linkage studies were performed on a large autosomal dominant family with Charcot-Marie-Tooth axonal neuropathy type 2 (CMT2) with 38 members of which 14 were affected. Onset of the disease was between 16 and 30 years of age with weakness and atrophy of the hands more severe than of the feet with slow progressive course in 12 patients. Deep tendon reflexes were absent in the upper extremities and decreased in the lower extremities.

Mutations of the noncoding region of the connexin32 gene in X-linked dominant Charcot-Marie-Tooth neuropathy.

We studied two families with X-linked dominant Charcot-Marie-Tooth neuropathy. The clinical findings included onset around age 14 years, with moderate weakness of feet extensors and palmar and dorsal interossei, areflexia, distal hypesthesia, and slow progressivity. Motor nerve conduction velocities showed slowing (20 to 30 m/sec) and EMGs were normal.

Correlation between connexin 32 gene mutations and clinical phenotype in X-linked dominant Charcot-Marie-Tooth neuropathy.

We studied the relationship between the genotype and clinical phenotype in 27 families with dominant X-linked Charcot-Marie-Tooth (CMTX1) neuropathy. Twenty-two families showed mutations in the coding region of the connexin32 (cx32) gene. The mutations include four nonsense mutations, eight missense mutations, two medium size deletions, and one insertion.

A Dejerine-Sottas neuropathy family with a gene mapped on chromosome 8.

The Patient is a 55-year-old black male who belongs to a large family with 9 affected relatives with autosomal dominant Dejerine-Sottas neuropathy (DSN). Onset of his condition was at 2 years of age with steppage gait followed by severe progressive weakness, atrophy, and sensory loss of his legs and hands accompanied by areflexia and thoracolumbar kyphoscoliosis. The patient became wheelchair confined at age 38.

Dejerine-Sottas disease with de novo dominant point mutation of the PMP22 gene.

We studied a 33-year-old woman with a negative family history. Both of her parents were examined clinically by nerve conduction velocities (NCVs) and EMG, with normal results. The clinical onset of her condition was at 24 months, with severe weakness and atrophy of her feet and hands, but the proximal muscles were relatively spared.

New point mutations and deletions of the connexin 32 gene in X-linked Charcot-Marie-Tooth neuropathy.

The purpose of this study was the identification of new mutations of the connexin 32 (CX32) gene in CMTX families. We report six new mutations of the CX32 gene including two medium sized (29 and 18 bp) deletions. The clinical phenotype is consistent with CMT peripheral neuropathy in all patients.

Point mutations of the connexin32 (GJB1) gene in X-linked dominant Charcot-Marie-Tooth neuropathy.

Ten families with X-linked dominant CMT neuropathy (CMTX1) were screened for point mutations of the connexin32 (Cx32, GJB1) gene. Two families showed missense mutations, respectively an A-->G transition at amino acid 102 (glutamate to glycine) and a C-->T transition at amino acid 142 (arginine to tryptophan). Three families showed nonsense mutations, respectively a C-->T transition at amino acid 22 (arginine to stop) a G-->T transversion at amino acid 186 (glutamate to stop), and a T-->A transversion at amino acid 217 (cysteine to stop).

Screening of dominantly inherited Charcot-Marie-Tooth neuropathies.

Sixty-three families with dominantly inherited Charcot-Marie-Tooth (CMT) neuropathies including 730 subjects (total) from which 356 affected were studied clinically, electrophysiologically (MNCVs and EMGs), by genetic linkage, and screened for DNA duplication. Thirty-eight families (60.3%) were type 1A (demyelinating CMT mapped on chromosome 17).

Charcot-Marie-Tooth neuropathy type 1A with both duplication and non-duplication.

We studied a family with nine of twenty members affected with Charcot-Marie-Tooth disease type 1A (CMT1A). The proband and her four affected sibs showed no duplication of the 17p11.2-p12 (CMT region).

Mapping of the gene for X-linked dominant Charcot-Marie-Tooth neuropathy.

We performed a clinical study and linkage analysis on 278 subjects (66 affected) belonging to eight families with X-linked dominant Charcot-Marie-Tooth (CMT) neuropathy. This form affects 11.8% of CMT patients in Iowa.

Charcot-Marie-Tooth neuropathy related to chromosome 1.

One family with documented male-to-male transmission of Charcot-Marie-Tooth (CMT) neuropathy was studied clinically and by genetic linkage. Patients had progressive distal weakness and atrophy, areflexia, and distal sensory loss, but early onset (before age 3 years) in all 5 cases, and phrenic nerve involvement in the propositus (a 39-year-old woman) requiring CPAP ventilator support during the night. Motor-nerve conduction velocities (MNCVs) were significantly slow, consistent with severe demyelinating neuropathy.

X-linked recessive Charcot-Marie-Tooth neuropathy: clinical and genetic study.

We describe three families with X-linked recessive Charcot-Marie-Tooth (CMT) neuropathies. The disease phenotype in family 1 was characterized by infantile onset, weakness of lower legs, areflexia, pes cavus, and mental retardation (2 of 5 patients). The disease phenotype in families 2 and 3 was characterized by late onset, distal weakness, and normal intelligence.

Heterogeneity in X-linked recessive Charcot-Marie-Tooth neuropathy.

Three families presenting with X-linked recessive Charcot-Marie-Tooth neuropathies (CMT) were studied both clinically and genetically. The disease phenotype in family 1 was typical of CMT type 1, except for an infantile onset; two of five affected individuals were mentally retarded, and obligate-carrier females were unaffected. Families 2 and 3 showed distal atrophy with weakness, juvenile onset, and normal intelligence.

Manifesting carrier of Becker muscular dystrophy (BMD): clinical and recombinant DNA studies.

We studied a Becker muscular dystrophy (BMD) family with a manifesting carrier. Proximal muscle weakness, pseudohypertrophy of the calves, significantly elevated serum creatine kinase and dystrophic alterations in the muscle biopsy were the characteristic phenotypical features of this manifesting carrier. The recombinant DNA study showed a recombinant chromosome with a crossover between pERT 87-8 and pERT J-Bir in the manifesting carrier.

Duchenne muscular dystrophy in monozygotic twins: deletion of 5' fragments of the gene.

A recombinant DNA study for deletion evaluation was performed in a 4 generation family with Duchenne muscular dystrophy (DMD) in twins. The patients were 6 years old, had a history of progressive difficulty in walking since age 4, and showed weak gluteals, iliopsoas, latissimus dorsi, rhomboids, lower trapezius, sternocleidomastoids, pseudohypertrophic calves, and tight heelcords. Both patients had high serum creatine kinase of 19,000 and 11,000 IU, respectively, and the muscle biopsy of the left vastus lateralis showed dystrophic alterations.

X-linked dominant Charcot-Marie-Tooth neuropathy with 15 cases in a family genetic linkage study.

A large CMT family with 5 affected males and 10 affected females of 37 members in four generations was investigated by recombinant DNA studies. The proband patient in his original description of the pedigree indicated male-to- male transmission in one of his relatives, suggesting autosomal dominant inheritance. The genetic linkage study between the CMT locus and the loci of six markers mapped on chromosome 1 (FY, APCS, AT3, REN, APOA2, and GBA) gave negative results.

Recombinant DNA study of Duchenne muscular dystrophy occurring in a myotonic dystrophy family.

A recombinant DNA study was performed in a three-generation family with 8 typical cases of late onset myotonic dystrophy (DM) and with one case of Duchenne muscular dystrophy (DMD). The study with DNA markers for chromosome 19 showed linkage of DM locus to the 3.8 Kb allele of apolipoprotein C2 (APOC2) probe and to 9 Kb allele of pSC11 probe (APOC2 lod score = 0.

Becker muscular dystrophy recombinant DNA studies in identical twins.

Two identical twins with Becker Muscular Dystrophy are reported. Both twins had the same red cell types for ABO, Rh, CDE, MNSs, Kelly, Lewis, Duffy, and Kidd. HLA typing detected the same antigens in both twins: A1, A26, B8, B17, DR3, DR7.

Evidence for linkage of Charcot-Marie-Tooth neuropathy (CMT1) to apolipoprotein A2 (Apo-A2).

We studied 169 members of 15 families with Charcot-Marie-Tooth neuropathy (CMT1) showing male-to-male transmission and slow motor-nerve conduction velocities. Four of these families were informative for linkage to apolipoprotein A2 on chromosome 1 (1q21-23) with an overall lod score of 2.45 at theta = .

Linkage analysis of Charcot-Marie-Tooth neuropathy (HMSN type I).

Fifteen HMSN families with 218 members and documented male-to-male transmission and slow motor nerve conduction velocities were informative for linkage to Duffy blood group (Fy), antithrombin III cDNA probe (AT3) and renin (REN). Our data support linkage to Fy in 8 families (lod score = 2.45 at theta = 0) consistent with HMSN type IB.