X-linked lethal infantile spinal muscular atrophy: From clinical description to molecular mapping
Abstract
The proximal spinal muscular atrophies (PSMA), one of the most common forms of lower motor neuron disease in children, are characterized by progressive muscle weakness due to loss of anterior horn cells. All three autosomal recessive forms have been mapped to chromosome 5q11.2-11.3, implying an allelic association between these disorders. Recent evidence from our laboratories, as well as others, suggests that a distinct form of lethal neonatal spinal muscular atrophy, associated with early onset contractures, is determined by a gene on the X chromosome. We report our efforts in mapping this disease locus. Our original studies have focused on two unrelated multigenerational families with similar clinical presentations of severe hypotonia, muscle weakness, and a disease course similar to Werdnig Hoffman except for the additional finding of congenital or early onset contractures. Muscle biopsy and/or autopsy were indicative of anterior horn cell loss in affected males. Disease occurrence in each of the families was consistent with an X-linked recessive mode of inheritance. Subsequently, two additional families have been identified, as well as several sporadic male cases. Linkage analysis has been completed in one of these families using highly polymorphic repeats dispersed 10 cM on the X chromosome. Interpretation of results wasmore »
- Authors:
-
- Univ. of Miami, FL (United States); and others
- Publication Date:
- OSTI Identifier:
- 134162
- Report Number(s):
- CONF-941009-
Journal ID: AJHGAG; ISSN 0002-9297; TRN: 95:005313-0898
- Resource Type:
- Journal Article
- Journal Name:
- American Journal of Human Genetics
- Additional Journal Information:
- Journal Volume: 55; Journal Issue: Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 55 BIOLOGY AND MEDICINE, BASIC STUDIES; NERVOUS SYSTEM DISEASES; AGE DEPENDENCE; LETHAL GENES; INFANTS; HEREDITARY DISEASES; PHENOTYPE; MUSCLES; GENETIC MAPPING; HUMAN CHROMOSOME 5; HUMAN X CHROMOSOME; BIOLOGICAL MARKERS; GENETICS; STATISTICS; RECESSIVE MUTATIONS; POLYMERASE CHAIN REACTION
Citation Formats
Baumbach, L, and Schiavi, A. X-linked lethal infantile spinal muscular atrophy: From clinical description to molecular mapping. United States: N. p., 1994.
Web.
Baumbach, L, & Schiavi, A. X-linked lethal infantile spinal muscular atrophy: From clinical description to molecular mapping. United States.
Baumbach, L, and Schiavi, A. 1994.
"X-linked lethal infantile spinal muscular atrophy: From clinical description to molecular mapping". United States.
@article{osti_134162,
title = {X-linked lethal infantile spinal muscular atrophy: From clinical description to molecular mapping},
author = {Baumbach, L and Schiavi, A},
abstractNote = {The proximal spinal muscular atrophies (PSMA), one of the most common forms of lower motor neuron disease in children, are characterized by progressive muscle weakness due to loss of anterior horn cells. All three autosomal recessive forms have been mapped to chromosome 5q11.2-11.3, implying an allelic association between these disorders. Recent evidence from our laboratories, as well as others, suggests that a distinct form of lethal neonatal spinal muscular atrophy, associated with early onset contractures, is determined by a gene on the X chromosome. We report our efforts in mapping this disease locus. Our original studies have focused on two unrelated multigenerational families with similar clinical presentations of severe hypotonia, muscle weakness, and a disease course similar to Werdnig Hoffman except for the additional finding of congenital or early onset contractures. Muscle biopsy and/or autopsy were indicative of anterior horn cell loss in affected males. Disease occurrence in each of the families was consistent with an X-linked recessive mode of inheritance. Subsequently, two additional families have been identified, as well as several sporadic male cases. Linkage analysis has been completed in one of these families using highly polymorphic repeats dispersed 10 cM on the X chromosome. Interpretation of results was achieved using an automated data acquisition program. Analysis of over 300 haplotypes generated using PCR-based DNA markers have identified two 16 cM regions on Xp with complete concordance to the disease phenotype. Our currents efforts are focused on the region surrounding the Kallman gene, in attempts to better define a candidate region, as well as analyze possible candidate genes within this region.},
doi = {},
url = {https://www.osti.gov/biblio/134162},
journal = {American Journal of Human Genetics},
number = Suppl.3,
volume = 55,
place = {United States},
year = {Thu Sep 01 00:00:00 EDT 1994},
month = {Thu Sep 01 00:00:00 EDT 1994}
}