Novel congenital myopathy locus identified in Native American Indians at 12q13.13-14.1

Abstract

This study reports the first gene mapping of Native American myopathy (NAM) using single-nucleotide polymorphism-based homozygosity mapping in only a few affected individuals from simplex families and identified a novel NAM locus. Identifying the genetic basis of NAM may suggest new genetic etiologies for other more common conditions such as congenital myopathy and malignant hyperthermia.

Stac3 is a component of the excitation–contraction coupling machinery and mutated in Native American myopathy

“…Given the myopathic features of mutants we explored whether stac3 mutations might cause congenital human myopathies. Human STAC3 mapped to chromosome 12q13–14, and its specific location was within the previously defined genetic locus for the congenital Native American myopathy (NAM) 24,25 . NAM is an autosomal recessive disorder found within the Lumbee Native American population of North Carolina that was characterized by a constellation of clinical features including congenital onset of muscle weakness, susceptibility to malignant hyperthermia, multiple joint contractures and dysmorphic facial features including ptosis.…”

“…The gene responsible for the mutant phenotype encoded for Stac3, a putative muscle specific adaptor protein. Finally we found that a missense mutation in human STAC3 is responsible for the debilitating, congenital Native American myopathy (NAM) 24,25 .…”

Clinicopathologic Conference: A Newborn With Hypotonia, Cleft Palate, Micrognathia, and Bilateral Club Feet

“…The variant p.W280S was originally described as c.1046G>C 9 , but is c.851G>C based upon the reference sequence ENST00000332782.6. Since the original description, several more cases have been reported with typical clinical features of short stature, cleft palate, myopathic facies, hypotonia, scoliosis and congenital joint contractures 10,11 , all of which are seen in our patient (Figure 1). In NAM there is a susceptibility to malignant hyperthermia, which is characterized by hyperthermia, muscle hyperactivity, rigidity, tachycardia/tachypnea, and metabolic acidosis in response to inhalation anesthetics and depolarizing muscle relaxants which also appeared to be present in our patient.…”

Cicatricial Alopecia in Identical Twin Lumbee Native American Women

“…Lumbee Indians trace their heritage back to Cheraw and Sioux Indians who settled in the southeastern region of North Carolina in the 1700s [3]. Several studies have shown certain diseases to be increased in the Lumbee population including congenital myopathy and glutaric acidemia type 1 [4,5]. Searching for MeSH terms “Lumbee” and “alopecia” did not reveal any results, nor did “Native American,” “alopecia,” or “hair loss.” Searching for the MeSH terms “alopecia” and “twins” reveals 23 results, mostly concerning alopecia areata and none regarding cicatricial alopecia.…”