title: Multiple congenital anomalies in two boys with mutation in HCFC1 and cobalamin disorder.
abstract: The cobalamin type C deficiency is a rare condition that results from impaired biosynthesis of both methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl). Hemizygous mutations of the HCFC1 gene explain the majority of clinically and biologically compatible cblC patients without MMACHC mutations (OMIM 309541). We report a family with two maternal half-brothers with multiple congenital anomalies and HCFC1 gene mutation in the second Kelch domain. Both presented with dysmorphic features (flat profile, cleft lip for one), increased nuchal translucency, prenatal onset microcephaly and hypospadias. Additionally to early onset intractable epilepsy and profound neurocognitive impairment, this familial observation suggests that HCFC1 gene should be considered in boys with midline malformations, even without proven cobalamin C deficiency.
authors.affiliation: Genetic Department, CHU Côte de Nacre, Caen, France. Electronic address: gerard-m@chu-caen.fr.
authors.forename: M
authors.initials: M
authors.lastname: Gérard
authors.affiliation: Genetic Department, CHU Amiens Picardie, France.
authors.forename: G
authors.initials: G
authors.lastname: Morin
authors.affiliation: Biochemistry, CHU Robert Debré, APHP, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Bourillon
authors.affiliation: Genetic Department, CHU Côte de Nacre, Caen, France.
authors.forename: C
authors.initials: C
authors.lastname: Colson
authors.affiliation: Neuropediatrics, Hôpital Trousseau, APHP, Paris, France; UPMC Sorbonne Universités, Univ Paris 06, France.
authors.forename: S
authors.initials: S
authors.lastname: Mathieu
authors.affiliation: Biochemistry, CHU Necker-Enfants Malades, APHP, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Rabier
authors.affiliation: Neuropediatrics, Hôpital Trousseau, APHP, Paris, France; UPMC Sorbonne Universités, Univ Paris 06, France.
authors.forename: T
authors.initials: T
authors.lastname: Billette de Villemeur
authors.affiliation: Reference Center for Metabolic Diseases, CHU Robert Debré, APHP, Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Ogier de Baulny
authors.affiliation: Biochemistry, CHU Robert Debré, APHP, Paris, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Benoist
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002675:Child, Preschool; D002971:Cleft Lip / Q000235:genetics; D003038:Cobamides / Q000096:biosynthesis; D055028:Comparative Genomic Hybridization; D005820:Genetic Testing; D051863:Host Cell Factor C1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007621:Karyotyping; D008297:Male; D009154:Mutation; D010088:Oxidoreductases; D014805:Vitamin B 12 / Q000031:analogs & derivatives / Q000096:biosynthesis; D014806:Vitamin B 12 Deficiency / Q000175:diagnosis / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D003038:Cobamides; C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; C019476:mecobalamin; C508359:MMACHC protein, human; D010088:Oxidoreductases; C000913:cobamamide; D014805:Vitamin B 12
keywords: Cleft lip and palate; HCFC1 gene; Hypospadias; Increased nuchal translucency; Multiple congenital malformations syndrome; X-linked cobalamin deficiency