Table 1.
Patient’s clinical presentation and BET1 variants identified.
| Family 1 | Family 2 | ||||
|---|---|---|---|---|---|
| P1 | P2 | P3 | |||
| Sex | Male | Female | Male | ||
| Age at time of death | 5 years | 4 months | 7 months | ||
| Pathogenic variants | |||||
| BET1 a |
c.202G>C; p. Asp68His Paternal (hg19) chr7:93623697C>G (hg38) chr7:93994385C>G |
c.134delC p. Ala45ValfsTer2 Maternal (hg19) chr7:93628492delG (hg38) chr7:93999180delG |
c.152T>G; p. Ile51Ser Homozygous (hg19) chr7:93625626A>C (hg38) chr7:93996314A>C |
||
| GnomAD AF b | 0 alleles | 29/28,198 alleles | 5/259550 alleles | ||
| CADD c | 27 | 34 | 32 | ||
| Clinical presentation | |||||
| Symptom Onset | Congenital: reduced fetal movements, hypotonia at birth | Congenital: hypotonia and tachypnea at birth | Congenital: hypotonia at birth | ||
| Neuromuscular | Severe and progressive weakness | Severe and progressive weakness, right‐sided brachial plexus palsy | Severe and progressive weakness | ||
| Respiratory | Respiratory insufficiency requiring nighttime non‐invasive ventilation (infancy) followed by ventilation via tracheostomy (4 years) | Respiratory failure (4 months) | Respiratory insufficiency (4 months) | ||
| Gastrointestinal | Feeding difficulties requiring gastrostomy tube | Feeding difficulties requiring gastrostomy tube | Feeding difficulties requiring gastrostomy tube | ||
| Ophthalmologic | Restricted extraocular movements, high myopia, bilateral cataracts | – | Poor tracking | ||
| Neurologic | Delayed speech with poor articulation, progressive, and refractory epilepsy (4 years) | – | – | ||
| CK (U/l) | 3,667–6,807 | 436–2,361 | 921–4,000s | ||
| Muscle Biopsy | Dystrophic. Reduced glycosylation of α‐dystroglycan (10 months) | NP | Myopathic | ||
| Electromyography | Myopathic (9 months) | Normal (3 weeks) | NP | ||
| Brain MRI | Normal (7 months), mild increase in T2‐ weighted white matter signal (28 months) | Normal (2 weeks) | Normal (4 days) | ||
| Bronchoscopy | NP | Mild tracheomalacia and mild bronchomalacia (4 months) | Severe glossoptosis, bronchomalacia, and oral secretions (4 months) | ||
| Echocardiogram | Normal | Normal | NP | ||
NP, not performed.
a
Transcript ID: NM_005868.6.
b
Genome aggregate database allele frequency.
c
Combined Annotation Dependent Depletion.