Identified KIF21A (NM_001173464.2) variants and associated clinical features
| Patient ID # | Family # | Gender/age at TOP | Affected gene | DNA change | Predicted AA change | Variant classification (ACMG) | Zygosity | OMIM phenotype (mode of inheritance) | Aetiological classification (OMIM diseases) | Prenatal abnormalities | Joint contractures | Dysmorphic features | Neurological abnormalities | Other features |
| F22:II.1 | 22 | M/TOP (24 WGA) | KIF21A | c.(1346T>A);(1346T>A) | p.((Leu449*));((Leu449*)) | Candidate gene, likely pathogenic | Homozygous | #135700 (AD), novel for AR pending | Likely neurogenic (disease name to be determined) | RFM, polyhydramnios, scalp oedema, pulmonary hypoplasia, missing stomach filling, diaphragmatic protrusion, thoracic kyphoscoliosis | Elbows, wrists, fingers, knees, ankles, talipes equinovarus (bilateral) | Hypertelorism, retrognathia, cleft palate, flat broad nose, low-set ears | Hypotrophy of lower leg muscles | Internally rotated shoulders, straight ribs, narrow long tubular bones |
| F22:II.2 | 22 | F/TOP (26 WGA) | KIF21A | c.(1346T>A);(1346T>A) | p.((Leu449*));((Leu449*)) | Candidate gene, likely pathogenic | Homozygous | #135700 (AD), novel for AR pending | Likely neurogenic (disease name to be determined) | RFM, polyhydramnios, IUGR, scalp oedema, thoracic hypoplasia, hydrothorax, ascites, missing stomach filling, diaphragmatic protrusion | Elbows, fingers, knees, talipes equinovarus (bilateral) | Microglossia, mircognathia and retrognathia, cleft palate, high-arched palate, low-set ears | − | Jejunal perforation, dilated tortuous ureter (bilateral), internally rotated shoulders, thoracic scoliosis, additional cervical rib, straight ribs, narrow long tubular bones, femoral anteversion (bilateral), genu recurvatum (bilateral) |
| F22:II.4 | 22 | M/TOP (21 WGA) | KIF21A | c.(1346T>A);(1346T>A) | p.((Leu449*));((Leu449*)) | Candidate gene, likely pathogenic | Homozygous | #135700 (AD), novel for AR pending | Likely neurogenic (disease name to be determined) | RFM, micrognathia, prenasal oedema, neck oedema, pulmonary hypoplasia | Knees, talipes equinovarus (bilateral) | ND (autopsy not performed) | − | − |
| F23:II.1 | 23 | M/TOP (29 WGA) | KIF21A | c.(2371del);(2371del) | p.((Arg791Glufs*8));((Arg791Glufs*8)) | Candidate gene, likely pathogenic | Homozygous | #135700 (AD), novel for AR pending | Likely neurogenic (disease name to be determined) | RFM, polyhydramnios, brachycephaly, scalp oedema, prenasal oedema, neck oedema, pulmonary hypoplasia, dextrocardia, gastrointestinal abnormalities | Fingers, wrists, talipes equinovarus (bilateral), rocker-bottom feet | Skull deformation with protruding skull bones, micrognathia and retrognathia, clinodactyly of 2nd digit (bilateral) | Cerebral ventriculomegaly | Severe pulmonary hypoplasia, dextrocardia, clenched hands with crossing fingers (bilateral) |
| F23:II.2 | 23 | F/TOP (28 WGA) | KIF21A | c.(2371del);(2371del) | p.((Arg791Glufs*8));((Arg791Glufs*8)) | Candidate gene, likely pathogenic | Homozygous | #135700 (AD), novel for AR pending | Likely neurogenic (disease name to be determined) | RFM, polyhydramnios, scalp oedema, prenasal oedema, pulmonary hypoplasia | Fingers, wrists, talipes equinovarus (bilateral) | Micrognathia and retrognathia (autopsy not performed) | − | − |
List of genetic variants and clinical details of individuals carrying bi-allelic variants in the candidate gene KIF21A. Provided information includes patient ID, family ID, gender, age at termination of pregnancy in WGA. Additionally, provided data include the affected gene, RefSeq ID, DNA change, AA change, variant classification (ACMG scores), gene-associated OMIM phenotype, mode of inheritance and zygosity.
The variant nomenclature is in accordance with Human Genome Variation Society standards.
AA, amino acid; ACMG, American College of Medical Genetics and Genomics; AD, autosomal dominant; AR, autosomal recessive; F, female; IUGR, intrauterine growth restriction; M, male; ND, no data; RFM, reduced fetal movements; TOP, termination of pregnancy; WGA, weeks of gestational age.