Renal agenesis (RA) is one of the more extreme examples of congenital anomalies of the kidney and urinary tract (CAKUT). Bilateral renal agenesis is almost invariably fatal at birth, and unilateral renal agenesis can lead to future health issues including end-stage renal disease. Genetic investigations have identified several gene variants that cause RA, including ,, and However, whereas compound null mutations of genes encoding α and γ retinoic acid receptors (RARs) cause RA in mice, to date there have been no reports of variants in RAR genes causing RA in humans. In this study, we carried out whole exome sequence analysis of two families showing inheritance of an RA phenotype, and in both identified a single candidate gene, Analysis of a zebrafish loss-of-function mutant revealed defects in the pronephric kidney just prior to death, and F0 CRISPR/Cas9 mutagenesis of in the mouse revealed kidney agenesis phenotypes, implicating in this disorder. GREB1L resides in a chromatin complex with RAR members, and our data implicate GREB1L as a coactivator for RARs. This study is the first to associate a component of the RAR pathway with renal agenesis in humans.

Foremilk and hindmilk contained comparable amounts of cobalamin and haptocorrin, but marked changes were observed during 9 mo of lactation. At 4 mo, low concentrations of milk cobalamin mirrored biochemical changes in infants, which suggests an impaired cobalamin status and indicates that nutrition from only mother's milk may not be sufficient for the supply of cobalamin from this age. This trial was registered by the Danish Data Protection Agency at www.datatilsynet.dk/english as 2008-41-2185.

Mandibulofacial dysostosis with microcephaly (MFDM) is a multiple malformation syndrome comprising microcephaly, craniofacial anomalies, hearing loss, dysmorphic features, and, in some cases, esophageal atresia. Haploinsufficiency of a spliceosomal GTPase, U5–116 kDa/EFTUD2, is responsible. Here, we review the molecular basis of MFDM in the 69 individuals described to date, and report mutations in 38 new individuals, bringing the total number of reported individuals to 107 individuals from 94 kindreds. Pathogenic EFTUD2 variants comprise 76 distinct mutations and seven microdeletions. Among point mutations, missense substitutions are infrequent (14 out of 76; 18%) relative to stop-gain (29 out of 76; 38%), and splicing (33 out of 76; 43%) mutations. Where known, mutation origin was de novo in 48 out of 64 individuals (75%), dominantly inherited in 12 out of 64 (19%), and due to proven germline mosaicism in four out of 64 (6%). Highly penetrant clinical features include, microcephaly, first and second arch craniofacial malformations, and hearing loss; esophageal atresia is present in an estimated ~27%. Microcephaly is virtually universal in childhood, with some adults exhibiting late “catch-up” growth and normocephaly at maturity. Occasionally reported anomalies, include vestibular and ossicular malformations, reduced mouth opening, atrophy of cerebral white matter, structural brain malformations, and epibulbar dermoid. All reported EFTUD2 mutations can be found in the EFTUD2 mutation database (http://databases.lovd.nl/shared/genes/EFTUD2).

Aneuploidy and subchromosomal aberrations can be detected using fetal cells harvested from maternal blood. The method has the future potential of being offered as a cell-based NIPT with large high genomic resolution.

In our previous studies, one-third of lactating Guatemalan women, infants, and children had deficient or marginal serum vitamin B-12 concentrations. Relationships among maternal and infant status and breast milk vitamin B-12, however, have not, to our knowledge, been investigated in such populations. Our purpose was to measure breast milk vitamin B-12 in Guatemalan women with a range of serum vitamin B-12 concentrations and explore associations between milk vitamin B-12 concentrations and maternal and infant vitamin B-12 intake and status. Participants were 183 mother-infant pairs breastfeeding at 12 mo postpartum. Exclusion criteria included mother <17 y, infant <11.5 or >12.5 mo, multiple birth, reported health problems in mother or infant, and mother pregnant >3 mo. Data collected on mothers and infants included anthropometry, serum and breast milk vitamin B-12, and dietary vitamin B-12. Serum vitamin B-12 concentrations indicated deficiency (<150 pmol/L) in 35% of mothers and 27% of infants and marginal status (150-220 pmol/L) in 35% of mothers and 17% of infants. In a multiple regression analysis, breast milk vitamin B-12 concentration was associated (P < 0.05) with both maternal vitamin B-12 intake (r = 0.26) and maternal serum vitamin B-12 (r = 0.30). Controlling for the number of breastfeeds per day and vitamin B-12 intake from complementary foods, infant serum vitamin B-12 was associated with maternal serum vitamin B-12 (r = 0.31; P < 0.001) but not breast milk vitamin B-12, implicating a long-term effect of pregnancy status on infant vitamin B-12 status at 12 mo postpartum.