Non-syndromic familial congenital anorectal malformations

Gene: FANCB

Green List (high evidence)

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Comment on phenotypes: Added phenotypes from OMIM and Gene2Phenotype

Created: 1 Nov 2018, 12:49 p.m.

Gene is on expert list from Dr Charles Shaw-Smith (Royal Devon and Exeter NHS Foundation Trust)

Created: 19 Sep 2018, 4:15 p.m.

Comment on list classification: Rating green as 3 unrelated cases of patients with variants in FANCB and VACTERL or VACTERL-like phenotypes that include anorectal malformations.

Created: 6 Sep 2018, 3:58 p.m.

FANCB is on the Illumina and UKGTN lists for VACTERL Association with Hydrocephalus and
Vacterl Association, X-Linked, With Or Without Hydrocephalus. Winberg et al 2014 (24416387) report a male fetus FC10, with anal atresia, a complex Fallot-like heart malformation, horseshoe kidney, bilateral rudimentary thumbs and a malformed right ear with atresia of the external auditory canal, in which a hemizygous 0.1–0.4 Mb deletion of the FANCB gene was identified. The mother was a healthy carrier. FC10 also had a 2.8 Mb-duplication on chromosome 16, dup(16)(p13.11p12.3). Mikat et al 2016 (PMID:26683739) report a case of an infant with VACTERL-H phenotype which included anal atresia. Sequencing of the FANCB gene in the mother and the affected male infant identified a heterozygous nonsense mutation in the mother (c.832C>T; p.Q278*) and the same hemizygous mutation in the patient. Watanabe et al 2017 (PMID: 29232005) report a case of X-linked VACTERL-H caused by deletion of exon 3 in FANCB. The patient's phenotype included imperforate anus. The mother had one copy of exon 3.

Created: 4 Aug 2018, 10:27 p.m.