Case#: male, onset at or before age 12 months, ethnicity not specified DiseaseAssertion: Patient is asserted to have both "SHORT syndrome" and "X-linked agammaglobulinemia (XLA)" due to "absence of peripheral B cells" and "features of SHORT syndrome such as hyperextensibility, vision abnormalities, lack of fat tissue, triangular face, extroverted ears, ocular depression, [and] developmental and teething delay" CasePresentingHPOs: HP:0000974 (Hyperextensible skin), HP:0000504 (Abnormality of vision), HP:0005320 (Lack of facial subcutaneous fat), HP:0000325 (Triangular face), HP:0000430 (Underdeveloped nasal alae), HP:0000490 (Deeply set eye), HP:0000750 (Delayed speech and language development), HP:0002719 (Recurrent infections), HP:0030084 (Clinodactyly), HP:0045075 (Sparse eyebrow), HP:0000540 (Hypermetropia), HP:0000696 (Delayed eruption of permanent teeth) CaseHPOFreeText: A current 9 year old was diagnosed with XLA with SHORT at age 15 months after presenting with skin lesions, scrotal swelling and ulcers along with recurring upper and lower tract infections after 6 months of age. Evaluations for immunodeficiencies were performed. Basic immunoglobulin levels and lymphocyte subsets were measured, which suggested an XLA diagnosis. Delays in developmental milestones observed by the mother and physical examination suggested SHORT syndrome. CaseNotHPOs: HP:0000558 (Rieger anomaly), HP:0000364 (Hearing abnormality) GenotypingMethod: Genotyping was performed by whole exome sequencing, whivh revealed a novel pathogenic homozygous frameshift mutation in the PIK3R1 gene. PreviouslyPublished: No prior article is known to contain information on the same proband. Variant: The patient harbors NM_181523.3:c.244dup(p.(lle82Asnfs24) chr5:67522740) variant in the homozygous state. ClinVar: This variant was not found in ClinVar CAID: This variant was not found in the ClinGen Allele Registry. gnomAD:* The variant was not found in gnomAD v4.1.0.

Case#: 36 y.o male European

DiseaseAssertion: Limb Girdle

FamilyInfo: None

CasePresentingHPOs: HP:0003701,HP:0003560, HP:0006785, HP:0003236,HP:0003325, HP:0008981,

CaseHPOFreeText: Experienced two episodes of atrial fibrillation. High CADD scores. Exercise-induced myalgia and/or rhabdomyolysis

CaseNotHPOs:

CaseNotHPOFreeText:

MotorAchievement: Age 20 he developed exercise intolerance and sporadic myoglobinuria after intense exercise. Able to walk and cycle for long distances with little muscle pain.

CreatineKinase: Ranging from 1700 to 8000 UI/L), at the age of 10 years

CasePreviousTesting: Last neurological examination there was moderate calf hypertrophy.

GenotypingMethod: Muscle Biopsy using next generation sequencing and multiple gene panel. Minimal myopathic changes on histological assessment and normal immunofluorescence staining for muscle proteins including α-sarcoglycan

PreviouslyPublished:

Variant: NM_000023.4(SGCA):c.850C>T (p.Arg284Cys)

ClinVar: 9439

CAID:

gnomAD: 0.0007716