Case Report: A Boy From a Consanguineous Family Diagnosed With Congenital Muscular Dystrophy Caused by Integrin Alpha 7 (ITGA7) Mutation

Abstract

Introduction: Congenital muscular dystrophy (CMD) is a group of early-onset disorders with clinical and genetic heterogeneity. Patients always present with muscle weakness typically from birth to early infancy, delay or arrest of gross motor development, and joint and/or spinal rigidity. There are various genes related to the development of CMD. Among them, mutations in integrin alpha 7 (ITGA7) is a rare subtype. The identification of disease-causing genes facilitates the diagnosis and treatment of CMD.Methods: We screened ITGA7 mutations in four people by whole exome sequencing and targeted sequencing from a consanguineous family. We then carried out electromyography and neuroelectrophysiological examinations to clarify a clinical picture of the patient diagnosed with CMD.Results: We report a Chinese boy diagnosed with CMD who carries a homozygous variant (c.1088dupG, p.H364Sfs*15) of the ITGA7 gene. According to the genotype analysis of his family members, this is an autosomal recessive inheritance.Conclusions: Our case further shows that ITGA7 mutation is related to CMD. Genetic counseling and multidisciplinary management of CMD play an important role in helping patients and their family. Further elucidation of the significant clinical and genetic heterogeneity, therapeutic targets, and the clinical care for patients remains our challenge for the future.

Dystroglycanopathies: Genetic Bases of Muscular Dystrophies Due to Alteration in the O-Glycosylation of α-Dystroglycan

“…These had various symptoms and different grades of severity. The consistent clinical features were muscle weakness and increased CK level [13].…”

“…Integrin α-7 deficient CMD: This CMD is caused by mutation in integrin α7 (ITGA7) and it is a rare subtype. This gene has 28 exons, among which 26 code for protein [13]. Only a few patients diagnosed with CMD were found to have ITGA7 mutation [6,[13][14][15][16] and it is not clear whether all variants are pathogenic mutations.…”

“…This gene has 28 exons, among which 26 code for protein [13]. Only a few patients diagnosed with CMD were found to have ITGA7 mutation [6,[13][14][15][16] and it is not clear whether all variants are pathogenic mutations. Variants of ITGA7 present microcephaly, agenesis of the corpus callosum, cerebellar hypoplasia, seizures, scoliosis, hemivertebrae, asymmetric extremities, and hypopigmented skin macules [16].…”

The role of the dystrophin glycoprotein complex in muscle cell mechanotransduction

“…Cardiac function was reportedly normal. 254 Point Mutations c.1506-2A>G Congenital muscular dystrophy with severe neurocognitive difficulties 145 DCM dilated cardiomyopathy, LGMD Limb-Girdle muscular dystrophy, WWS Walker-Warburg syndrome, XLCM X-Linked cardiomyopathy. …”

Integrin α7 Mutations Are Associated With Adult‐Onset Cardiac Dysfunction in Humans and Mice

“…Some studies have described skeletal muscle pathology or dysfunction in patients and mice lacking integrin α7, but these only involved a limited number of patients with ITGA7 deficiency with pediatric clinical presentations. 26 , 27 , 28 , 29 , 30 , 31 Only 1 study has reported a proband carrying variants in ITGA7 and MYH7 (myosin heavy chain beta) genes with features of cardiomyopathy. 29 Other family members demonstrating isolated cardiomyopathy only carried the MYH7 variant, and therefore the role of integrin α7 in cardiac function remains unknown.…”