These patients are born to consanguineous parents of Moroccan origin, which are both heterozygous for this mutation (Fig. 1C) and are not related to patient TTD218UT. Patient TTD241HE was diagnosed at 18 months of age with brittle hair (tiger-tail banding pattern), dysmorphic features, developmental delay, moderate intellectual disability, microcephaly, difficulty swallowing and failure to thrive, cheerful character, mild Ichthyosis, growth retardation (length −4.7 SD, weight −2.6 SD), occipitofrontal circumference (OFC) (−3.1 SD), hypertonia, microcytic hypochromic anemia and recurrent infections. At 6 years of age, she still showed spasticity, ataxia and mild cognitive retardation without significant speech, but no signs of progressive deterioration. She has one affected younger sib (TTD275HE), also diagnosed with brittle hair, dysmorphic features, mild developmental delay, microcephaly, mild difficulty swallowing, no failure to thrive, cheerful character, mild ichthyosis, additional left thumb, no recurrent infections and growth retardation were noticed.
Case: TTD241HE
CaseDemographics: Female, diagnosis at 18 months, Moroccan origin
CasePresentingHPOs: HP:0002299, HP:0045055, HP:0001999, HP:0001263, HP:0002342, HP:0000252, HP:0200136, HP:0001508, HP:0008064, HP:0008897, HP:0001276, HP:0004840, HP:0001257, HP:0002497,
cheerful character, mild ichthyosis, length −4.7 SD, weight −2.6 SD, occipitofrontal circumference (OFC) −3.1 SD, recurrent infections, mild cognitive retardation without significant speech at 6 years of age.
CaseNOTHPOs: No progressive deterioration at age 6
CasePreviousTesting: None
CaseGenotypingMethod: Sanger sequencing of the TFIIE subunits
Variant: NM_002095.5(GTF2E2):c.559G>T (p.Asp187Tyr)
ClinVar ID: 225841
Pathogenic, non-LOF variant gnomAD: Not found in gnomAD
AddCaseInfo: The parents of this individual were consanguineous and of Moroccan origin and were found to be heterozygous carriers of the variant. The individual's younger sister (TTD275HE) was also affected and homozygous for this variant. She also presented with brittle hair, dysmorphic features, mild developmental delay, microcephaly, mild difficulty swallowing, no failure to thrive, cheerful character, mild ichthyosis, additional left thumb, no recurrent infections and growth retardation
VariantEvidence: This variant has been identified in two other individuals (other than this proband and her sibling) of Moroccan origin, giving rise to the question of a founder mutation. This proband is not being scored since the variant has already been awarded default points previously.