Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients.

De novo germline variants in several components of the SWI/SNF-like BAF complex can cause Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NCBRS), and nonsyndromic intellectual disability. We screened 63 patients with a clinical diagnosis of CSS for these genes (ARID1A, ARID1B, SMARCA2, SMARCA4, SMARCB1, and SMARCE1) and identified pathogenic variants in 45 (71%) patients. We found a high proportion of variants in ARID1B (68%).

Keratosis Follicularis Spinulosa Decalvans is caused by mutations in MBTPS2.

Keratosis Follicularis Spinulosa Decalvans (KFSD) is a rare genetic disorder characterized by development of hyperkeratotic follicular papules on the scalp followed by progressive alopecia of the scalp, eyelashes, and eyebrows. Associated eye findings include photophobia in childhood and corneal dystrophy. Due to the genetic and clinical heterogeneity of similar disorders, a definitive diagnosis of KFSD is often challenging.

Recurrent somatic mosaicism for D4Z4 contractions in a family with facioscapulohumeral muscular dystrophy.

Autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) is caused by contraction of the D4Z4 repeat on 4q35. We describe a FSHD family of unusual genetic complexity presenting with two independent mitotic contractions of D4Z4 in two successive generations. In addition, a non-pathogenic FSHD-sized allele of approximately the same size is interfering with the DNA diagnosis in this family.

Somatic mosaicism in FSHD often goes undetected.

Autosomal dominant facioscapulohumeral muscular dystrophy (FSHD1A) is associated with contractions of the polymorphic D4Z4 repeat array on chromosome 4qter. The disease has a high frequency of new mutations of mitotic origin. Pulsed-field gel electrophoresis-based studies show that mitotic mutations leading to somatic mosaicism occur equally frequently in patients and parents.