- Mar 2021
affected boy (IV-1; 11 years)
Case#: IV-1, male, 11 y.o, Pakistani
DiseaseAssertion: Limb-girdle muscular dystrophy (LGMD2F), sarcoglycanopathy
FamilyInfo: Consanguineous parents, both described as healthy and showing no abnormality. Three unaffected siblings were also reported: IV-2 (male, 10 y.o), IV-4 (male, 7 y.o), and IV-5 (female, 1.5 y.o). A deceased sister is included on the pedigree, but no details about this individual were reported. See Figure 1.
CasePresentingHPOs: HP:0001288, HP:0002650, HP:0003547, HP:0003749, HP:0001655
CaseHPOFreeText: Reduced weight gain noted at 3-4 y.o. Mild cardiac hypertrophy observed on cardiac review (additional echocardiography results reported in "Echocardiography" section). Additional phenotypic information reported in Supplementary Table 1.
CaseNotHPOs: HP:0009077, HP:0000703, HP:0001382, HP:0000365, HP:0001510, HP:0001249, HP:0000478, HP:0030148, HP:0011675
CaseNotHPOFreeText: Extensor muscles of the wrist, toes flexors, and hip abductors noted to be relatively normal. Additional phenotypic information reported in Supplementary Table 1.
MotorAchievement: Sat without assistance at 8 months of age, walked at 15 months of age, ran at 1.5 months of age. Never jumped or hopped. Frequent falls noted, as well as difficulty in walking and climbing stairs since 3 y.o.
CreatineKinase: 18SU (normal: 20SU for children, 10SU for adults) (see Supplementary Table 1). No assertion was made by the authors regarding whether this represents a normal or decreased CK level.
PreviousTesting: Thyroid stimulating hormone: 2.3mU/L (normal: <0.6mU/L); Serum VZV IgG: 286mlU/ml (normal: >150mlU/ml); IGF-1:186 ng/μl (normal: 102-520 ng/μl for males, 14 y.o); PRL: 202 ng/dl (normal: 42.5-414 ng/dl for males); Vitamin D: 47nmol/L (normal: 25-50 nmol/L); Free T4: 17.0 pmol/L (normal:10.8-19.0 pmol/L) (see Supplementary Table 1)
GenotypingMethod: (1) Targeted next generation sequencing of 31 genes associated with LGMD from proband genomic DNA extracted from peripheral blood sample; (2) Sanger sequencing of genomic DNA extracted from peripheral blood samples to confirm SGCD variant of interest in proband and three family members (III-3, III-4, IV-4). Variant was identified in homozygosity in the proband, in heterozygosity in each of the parents, and was not present in the unaffected sibling (IV-4).
Variant: NM_000337.5:c.289C>T (p.Arg97Ter)
gnomAD: Not reported
- Jan 2021
CaseAJV: 17 years diagnosis, Australia
DiseaseAssertion: Hypertrophic Cardiomyopathy
FamilyInfo: Father (index case) died awaiting cardiac transplant (carried both variants). Two possibly affected relatives.
CasePresentingHPOs: HP:0001639, HP:0006536
(Hypertrophic cardiomyopathy, Obstructive lung disease)
HPOsFreeText: Maximum left ventricular hypertrophy at 17 mm, Sudden cardiac death event at 17 years, Maximal wall thickness at 22mm,
CasePreviousTesting: See Table 1
CaseGenotypingMethod: DNA was isolated from peripheral blood. Most participants underwent testing from the Illumina Cardiomyopathy Sequencing Panel, which includes 46 cardiomyopathy related genes. For others, whole exome sequencing or Sanger squencing was used. After the results were returned, variants were filtered for pathogenicity and rarity.
gnomAD: Not in gnomAD
Multiple Gene Variants:
Variant: NM_000256.3:c.2980C>T (p.Leu994Phe)
gnomAD: European (Non-Finnish) 1.624e-4, Overall 8.461e-5 https://gnomad.broadinstitute.org/variant/11-47355487-G-A