Table 1 High-chance results reported in BabyScreen+ and their clinical impact
From: Feasibility, acceptability and clinical outcomes of the BabyScreen+ genomic newborn screening study
Gene | Condition and mode of inheritance | Case number and sex | Variant(s) | Variant classification | Inheritance | Clinical assessment and impact |
|---|---|---|---|---|---|---|
Prevention | ||||||
G6PD | G6PD deficient hemolytic anemia, MONDO 0005775, X-linked recessive | 1M and 2M | NM_000402.4: c.1039G>A (p.Glu347Lys) | Pathogenic | Maternal | • Information provided on triggers of hemolytic crisis. • Alerts placed in hospital medical records and primary care physician notified. • Ten family members diagnosed. • No history of hemolytic crises in any of the families. |
3M and 4M | NM_001360016.2:c.1376G>T (p.Arg459Leu) | Pathogenic | Maternal | |||
5M | NM_000402.4:c.1093G>A (p.Ala365Thr) | Pathogenic | Maternal | |||
6M | NM_001360016.2:c.542A>T (p.Asp181Val) | Pathogenic | Maternal | |||
MT-RNR1 | Mitochondrial nonsyndromic sensorineural hearing loss, MONDO 0010779, mitochondrial | 7F | NC_012920.1:m.1494C>T (homoplasmic) | Likely pathogenic | Maternal | • Information provided on avoidance of aminoglycoside exposure. • Alerts placed in hospital medical records and primary care physician notified. • One family member diagnosed (normal hearing). • Passed newborn hearing screening, audiology assessment at 6 months of age for proband and mother. |
8M | NC_012920.1:m.1555A>G (48% heteroplasmy) | Pathogenic | Maternal | • Information provided on avoidance of aminoglycoside exposure. • Alerts placed in hospital medical records and primary care physician notified. • Passed newborn hearing screening, audiology assessment recommended if concerns arise regarding hearing. | ||
RYR1 | Malignant hyperthermia susceptibility 1, MONDO 0007783, autosomal dominant | 9M | NM_000540.3:c.1202G>T (p.Arg401Leu) | Likely pathogenic | Paternal | • Information provided on avoidance of suxamethonium and volatile anesthetic agents. • Alerts placed in hospital medical records and primary care physician notified. • Three family members diagnosed (no history of anesthetic events). |
Surveillance | ||||||
FBN1 | Marfan syndrome, MONDO 0007947, autosomal dominant | 10F | NM_000138.5:c.5518C>T (p.Arg1840Cys) | Likely pathogenic | Maternal | • Echocardiogram and regular cardiology review. • Two family members diagnosed, referred for surveillance, adult family member had phenotypic features of Marfan syndrome. |
GNASa | Pseudohypoparathyroidism 1a, MONDO 0007078, autosomal dominant (imprinted) | 11M | NM_000516.7:c.476T>C (p.Val159Ala)b | Pathogenic | Maternal | • Also identified by standard NBS with hypothyroidism. • Treatment with thyroxine, endocrinology assessment. • Two family members diagnosed, referred to endocrinology, one had brachydactyly, normal intellect. |
ENG | Hereditary hemorrhagic telangiectasia type 1, MONDO 0008535, autosomal dominant | 12F | NM_001114753.3:c.1310G>A (p.Arg437Gln) | Likely pathogenic | Paternal | • MRI for cerebral arteriovenous malformations. Referral to hereditary hemorrhagic telangiectasia clinic for ongoing surveillance. • One family member diagnosed with history of epistaxis, referred to adult hereditary hemorrhagic telangiectasia clinic. |
GJB2 | Autosomal recessive nonsyndromic hearing loss 1A, MONDO 0009076 | 13M | NM_004004.6:c.35del (p.Gly12Valfs*2) NM_004004.6:c.583A>G (p.Met195Val) | Pathogenic | Biparental | • Passed newborn hearing screening. • Referred for annual audiology assessments. |
DICER1 | DICER1-related tumor predisposition, MONDO 0100216, autosomal dominant | 14M | NM_177438.3:c.745C>T (p.Gln249*) | Pathogenic | Paternal | • Referred to pediatric oncologist for regular surveillance. Lung lesion currently under investigation. • One family member diagnosed, referred to adult familial cancer center. • Family history of thyroid adenoma. |
Treatment | ||||||
PHKB | Glycogen storage disease IXb, MONDO 0009868, autosomal recessive | 15M | NM_000293.3:c.1127-2A>G (homozygous) | Pathogenic | Biparental | • Admission to hospital for unrelated cardiac surgery, protocol to avoid hypoglycemia during fasting followed. • Liver ultrasound. |
UNC13Dc | Familial hemophagocytic lymphohistiocytosis 3, MONDO 0012146, autosomal recessive | 16F | NM_199242.2:c.817C>T (p.Arg273*) NM_199242.3:c.627del (p.Val210Trpfs*39) | Pathogenic | Biparental | • Immunological tests (lymphocyte subsets, immunoglobulins and soluble CD25) abnormal at time of results, increased ferritin. • Admitted to hospital for treatment with steroids and Emapalumab. • Bone marrow transplant. • Parents had undergone expanded carrier screening, UNC13D not included in panel |
