DISP1 deficiency: Monoallelic and biallelic variants cause a spectrum of midline craniofacial malformations.

Purpose: DISP1 encodes a transmembrane protein that regulates the secretion of the morphogen, Sonic hedgehog, a deficiency of which is a major cause of holoprosencephaly (HPE). This disorder covers a spectrum of brain and midline craniofacial malformations. The objective of the present study was to better delineate the clinical phenotypes associated with division transporter dispatched-1 (DISP1) variants.

FOSL2 truncating variants in the last exon cause a neurodevelopmental disorder with scalp and enamel defects.

Purpose: We aimed to investigate the molecular basis of a novel recognizable neurodevelopmental syndrome with scalp and enamel anomalies caused by truncating variants in the last exon of the gene FOSL2, encoding a subunit of the AP-1 complex.

Methods: Exome sequencing was used to identify genetic variants in all cases, recruited through Matchmaker exchange. Gene expression in blood was analyzed using reverse transcription polymerase chain reaction.

Fetal Description of the Pancreatic Agenesis and Holoprosencephaly Syndrome Associated to a Specific Variant.

Holoprosencephaly (HPE) is a clinically and genetically heterogeneous disease, which can be associated with various prenatal comorbidities not always detectable on prenatal ultrasound. We report on the case of a foetus carrying a semi-lobar HPE diagnosed at ultrasound, for which a fetal autopsy and a whole exome sequencing were performed following a medical termination of pregnancy. Neuropathological examination confirmed the semi-lobar HPE and general autopsy disclosed a total pancreas agenesis.

Meiotic genes in premature ovarian insufficiency: variants in HROB and REC8 as likely genetic causes.

Premature ovarian insufficiency (POI), affecting 1 in 100 women, is characterised by loss of ovarian function associated with elevated gonadotropin, before the age of 40. In addition to infertility, patients face increased risk of comorbidities such as heart disease, osteoporosis, cancer and/or early mortality. We used whole exome sequencing to identify the genetic cause of POI in seven women.