Muscular dystrophy and myopathy_Paediatric

Gene: COL4A1

Green List (high evidence)

Genereviews PMID: 20301768

Variants associated with hereditary angiopathy, nephropathy, aneurysms, and muscle cramps (i.e., HANAC syndrome) are localized in exons 24 and 25, affecting glycine residues.

Whereas all but one pathogenic variant responsible for more severe brain disease, including porencephaly and small-vessel brain disease, are mostly distributed through exons 25 to 51.

Created: 3 May 2022, 11:57 p.m. | Last Modified: 3 May 2022, 11:57 p.m.

Panel Version: 0.13662

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps MIM#611773; Brain small vessel disease with or without ocular anomalies MIM#175780; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant MIM#618564

Publications

• 24628545
• 25719457
• 21625620
• 23225343
• 23065703
• 20818663
• 20301768

Variants in this GENE are reported as part of current diagnostic practice

I don't know

PMID: 25719457 - only 2/137 heterozygous patients were described with myopathy, both had postnatal onset and Gly-X-Y missense variants. One of these patients also had muscle atrophy. Most patients had either periventricular leukoencephalopathy or porencephaly

PMID: 21625620 - two patients with muscle-eye-brain disease (MEB) and Walker-Warburg syndrome (WWS). Both patients were had heterozygous missense mutations but neither affected Gly within the G-X-Y repeat. One variant was functionally similar to DN G-X-Y variants. One patient was reported with congenital muscular dystrophy, the other showed progressive weakening from 1 year of age.

PMID: 23225343 - 1/15 leukoencephalopathy patients reported with myopathy, patient was 12 years old and heterozygous for a splice variant proven to result in either an inframe delins or a PTC. Myopathy specificity not reported.

Summary: myopathy is rarely reported, dystrophy less so

Created: 22 Jun 2020, 5:19 a.m. | Last Modified: 22 Jun 2020, 5:19 a.m.

Panel Version: 0.15

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Microangiopathy and leukoencephalopathy, pontine, autosomal dominant 618564; Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps 611773

Publications

• PMID: 25719457
• 21625620
• 23225343

I don't know

At least 2 cases reported with a myopathy, but it isn't a frequent feature of the condition. Mouse model has myopathic features.
Sources: Expert Review

Created: 24 Feb 2020, 4:08 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps MIM#611773; Brain small vessel disease with or without ocular anomalies MIM#175780

Publications

• 25719457
• 31051113

Green List (high evidence)

Loss of function by frameshift and splice variants (PMID:23065703); dominant negative by missense variants in the collagen domains (PMID:16159887).
Incomplete penetrance has been reported (PMID:21625620).

Created: 9 Jan 2020, 6:46 a.m. | Last Modified: 9 Jan 2020, 6:46 a.m.

Panel Version: 0.1

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
?Retinal arteries, tortuosity of MIM#180000; Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps MIM#611773; Brain small vessel disease with or without ocular anomalies MIM#175780; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant MIM#618564

Publications

• 23065703
• 20818663

Mode of pathogenicity
Other