Search

PurposeTo describe our experience of offering simultaneous genetic carrier screening for cystic fibrosis (CF), fragile X syndrome (FXS), and spinal muscular atrophy (SMA).MethodsCarrier screening is offered through general practice, obstetrics, fertility, and genetics settings before or in early pregnancy. Carriers are offered genetic counseling with prenatal/preimplantation genetic diagnosis available to those at increased risk.ResultsScreening of 12,000 individuals revealed 610 carriers (5.08%; 1 in 20): 342 CF, 35 FXS, 241 SMA (8 carriers of 2 conditions), approximately 88% of whom had no family history. At least 94% of CF and SMA carriers' partners were tested. Fifty couples (0.42%; 1 in 240) were at increased risk of having a child with one of the conditions (14 CF, 35 FXS, and 1 SMA) with 32 pregnant at the time of testing. Of these, 26 opted for prenatal diagnosis revealing 7 pregnancies affected (4 CF, 2 FXS, 1 SMA).ConclusionThe combined affected pregnancy rate is comparable to the population risk for Down syndrome, emphasizing the need to routinely offer carrier screening. The availability of appropriate genetic counseling support and a collaborative approach between laboratory teams, genetics services, health professionals offering screening, and support organizations is essential.

We provide the first description of a patient with a heterozygous deletion of the Attractin-like (ATRNL1) gene. The patient presented with a novel and distinctive phenotype comprising dysmorphic facial appearance, ventricular septal defect, toe syndactyly, radioulnar synostosis, postnatal growth retardation, cognitive impairment with autistic features, and ataxia. A 325 kb de novo deletion in ATRNL1 was demonstrated using SNP microarray and confirmed by FISH analysis using BAC probes. Sequence analysis of the undeleted allele did not identify any alterations, suggesting that the phenotype was the result of haploinusfficiency. ATRNL1 and its paralog ATRN are highly conserved transmembrane proteins thought to be involved in cell adhesion and signalling events. The phenotype of mice with homozygous Atrn mutations overlaps considerably with the features observed in our patient. We therefore postulate that our patient’s phenotype is caused by the deletion of ATRNL1, and provide further insight into the role of ATRNL1 in human development.