Recessive and dominant mutations in COL12A1 cause a novel EDS/myopathy overlap syndrome in humans and mice

Five families with mEDS have been reported: four with autosomal dominant and one with autosomal recessive inheritance.

“So far, five families have been reported: four with an autosomal dominant condition and one with an autosomal recessive condition.”

Through these studies they identified eight patients in four families that presented with autosomal recessive (two patients, one family) and dominant (six patients, three families) forms of EDS/myopathy.

“Through these studies they identified eight patients in four families that presented with autosomal recessive (two patients, one family) and dominant (six patients, three families) forms of EDS/myopathy.”

To date, nine patients from five families with myopathic EDS have been reported.

“To date, nine patients from five families with myopathic EDS have been reported [Hicks et al., 2014;Zou et al., 2014;Punetha et al., 2016]”

The siblings reported by Zou et al. [2014] (homozygous mutation) had the most severe phenotype with profound muscle hypotonia at birth, poor feeding and swallowing, and night-time hypoventilation, with need for tube feeding and non-invasive night-time ventilation.

“The siblings reported by Zou et al. [2014] (homozygous mutation) had the most severe phenotype with profound muscle hypotonia at birth, poor feeding and swallowing, and night-time hypoventilation, with need for tube feeding and non-invasive night-time ventilation.”

The affected siblings from the family with autosomal recessive mEDS have a more severe form than patients with autosomal dominant inheritance.

“The affected siblings from the family with the autosomal recessive condition have a more severe form of the condition than patients with autosomal dominant inheritance [Zou et al., 2014].”

Zou et al. [2014] and Hicks et al. [2014] investigated groups of patients that had some symptoms of these myopathies but presented with a distinctive phenotype and did not have mutations affecting type VI collagen.

“Zou et al. [2014] andHicks et al. [2014] investigated groups of patients that had some symptoms of these myopathies but presented with a distinctive phenotype and did not have mutations affecting type VI collagen.”

Collagen XII is found along the surfaces of the fibers of collagen type I in tissues that express that collagen, and it is presumed to act as a bridge between the collagen I fibers and other extracellular components including decorin, fibromodulin, and TNX.

“It is found along the surfaces of the fibers of collagen type I in tissues that express that collagen, and it is presumed to act as a bridge between the collagen I fibers and other extracellular components including decorin, fibromodulin, and TNX [Zou et al., 2014].”

There appears to be a mild phenotype (dominant) in carriers and a severe phenotype (recessive) in individuals that are homozygous for the autosomal recessive myopathic EDS mutation.

“Reportedly carrier parents walked late (almost at 2 years of age); therefore there appears to be a mild phenotype (dominant) in the carriers and a severe phenotype (recessive) in the individuals that are homozygous [Zou et al., 2014].”

The siblings reported by Zou et al. [2014] had a severe delay in motor development, and they eventually were able to reach a sitting position, but were never able to stand or walk.

“They had a severe delay in motor development, and they eventually were able to reach a sitting position, but were never able to stand or walk [Zou et al., 2014].”

Their age at publication ranged from birth to 48 years.

“Their age at publication ranged from birth to 48 years (Table S1) [Hicks et al., 2014;Zou et al., 2014;Punetha et al., 2016].”