Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0700208 (scoliosis)
 8,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations in the LMNA gene result in diverse phenotypes including Emery Dreifuss muscular dystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy with conduction system disease, Dunnigan type familial partial lipodystrophy, mandibulo acral dysplasia, Hutchinson Gilford progeria syndrome, restrictive dermopathy and autosomal recessive Charcot Marie Tooth type 2. The c.1930C > T (R644C) missense mutation has previously been reported in eight unrelated patients with variable features including left ventricular hypertrophy, limb girdle muscle weakness, dilated cardiomyopathy and atypical progeria. Here we report on the details of nine additional patients in eight families with this mutation. Patients 1 and 2 presented with lipodystrophy and insulin resistance, Patient 1 having in addition focal segmental glomerulosclerosis. Patient 3 presented with motor neuropathy, Patient 4 with arthrogryposis and dilated cardiomyopathy with left ventricular non-compaction, Patient 5 with severe scoliosis and contractures, Patient 6 with limb girdle weakness and Patient 7 with hepatic steatosis and insulin resistance. Patients 8 and 9 are brothers with proximal weakness and contractures. Nonpenetrance was observed frequently in first degree relatives. This report provides further evidence of the extreme phenotypic diversity and low penetrance associated with the R644C mutation. Possible explanations for these observations are discussed.
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PMID:Extreme phenotypic diversity and nonpenetrance in families with the LMNA gene mutation R644C. 1847 90

Merosin deficient congenital muscular dystrophy type 1A (MDC1A) is caused by defects in the LAMA2 gene. Patients with MDC1A exhibit severe symptoms, including congenital hypotonia, delayed motor development and contractures. The present case report describes a Vietnamese male child with clinical manifestations of delayed motor development, limb-girdle muscular dystrophy, severe scoliosis and white matter abnormality in the brain. Whole exome sequencing (WES) was performed with subsequent validation using Sanger sequencing, and a de novo missense variant (NM_000426.3:c.1964T>C, p.Leu655Pro) and a splice site variant (NG_008678.1:c.3556-13T>A) in the LAMA2 gene of the proband was detected. The missense variant located in exon 14 and has not been reported previously, to the best of our knowledge; whereas the splice site variant has been previously reported to cause premature termination of transcription in patients with MDC1A. In silico tools predicted that the missense variant was damaging. Phenotype-genotype analysis suggested that this proband was associated with classical early onset MDC1A. The co-existence of a de novo and a heterozygous variant in the LAMA2 gene suggested that the de novo variant contributed to the autosomal recessive manner of the disease. Careful consideration of this event by clinical confirmation of parental carrier status may help to accurately determine the risk of occurrence of this disease in future offspring. Additionally, WES is recommended as a powerful tool to assist in identifying potentially causative variants for heterogeneous diseases such as MDC1A.
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PMID:A novel de novo variant of LAMA2 contributes to merosin deficient congenital muscular dystrophy type 1A: Case report. 3192 73